Skip to main content
Top
Published in: Cancer and Metastasis Reviews 3-4/2012

01-12-2012

The rejuvenated scenario of epithelial–mesenchymal transition (EMT) and cancer metastasis

Authors: Fanyan Meng, Guojun Wu

Published in: Cancer and Metastasis Reviews | Issue 3-4/2012

Login to get access

Abstract

The molecular mechanisms underlying cancer progression and metastasis are still poorly understood. In recent years, the epithelial-to-mesenchymal transition (EMT), a traditional phenomenon revealed in embryonic development, has been gradually accepted as a potential mechanism underlying cancer progression and metastasis. Many cell signaling pathways involved in development have been shown to contribute to EMT. An increasing number of genetic and epigenetic elements have been discovered, and their cross-talk relationship in EMT remains to be explored. In addition, accumulating experimental evidence suggests that EMT plays a critical role in different aspects of cancer progression, such as metastasis, stem cell traits, and chemoresistance. However, there are some disagreements and debate about these studies, which raise critical questions worthy of further investigation. Solving these questions will lead to a more complete understanding of cancer metastasis. Due to the close relationship of EMT to cancer metastasis and chemoresistance, targeting EMT or reversing EMT is likely to lead to novel therapeutic approaches for the treatment of human cancers.
Literature
2.
go back to reference Baum, B., Settleman, J., & Quinlan, M. P. (2008). Transitions between epithelial and mesenchymal states in development and disease. Seminars in Cell & Developmental Biology, 19(3), 294–308. doi:10.1016/j.semcdb.2008.02.001. Baum, B., Settleman, J., & Quinlan, M. P. (2008). Transitions between epithelial and mesenchymal states in development and disease. Seminars in Cell & Developmental Biology, 19(3), 294–308. doi:10.​1016/​j.​semcdb.​2008.​02.​001.
4.
go back to reference Thiery, J. P., & Sleeman, J. P. (2006). Complex networks orchestrate epithelial–mesenchymal transitions. Nature Reviews Molecular Cell Biology, 7(2), 131–142. doi:10.1038/nrm1835.PubMed Thiery, J. P., & Sleeman, J. P. (2006). Complex networks orchestrate epithelial–mesenchymal transitions. Nature Reviews Molecular Cell Biology, 7(2), 131–142. doi:10.​1038/​nrm1835.PubMed
6.
go back to reference Davies, J. A. (1996). Mesenchyme to epithelium transition during development of the mammalian kidney tubule. Acta Anat (Basel), 156(3), 187–201. Davies, J. A. (1996). Mesenchyme to epithelium transition during development of the mammalian kidney tubule. Acta Anat (Basel), 156(3), 187–201.
7.
go back to reference Voulgari, A., & Pintzas, A. (2009). Epithelial–mesenchymal transition in cancer metastasis: Mechanisms, markers and strategies to overcome drug resistance in the clinic. Biochimica et Biophysica Acta, 1796(2), 75–90. doi:10.1016/j.bbcan.2009.03.002.PubMed Voulgari, A., & Pintzas, A. (2009). Epithelial–mesenchymal transition in cancer metastasis: Mechanisms, markers and strategies to overcome drug resistance in the clinic. Biochimica et Biophysica Acta, 1796(2), 75–90. doi:10.​1016/​j.​bbcan.​2009.​03.​002.PubMed
8.
go back to reference Barr, S., Thomson, S., Buck, E., Russo, S., Petti, F., Sujka-Kwok, I., et al. (2008). Bypassing cellular EGF receptor dependence through epithelial-to-mesenchymal-like transitions. Clinical & Experimental Metastasis, 25(6), 685–693. doi:10.1007/s10585-007-9121-7. Barr, S., Thomson, S., Buck, E., Russo, S., Petti, F., Sujka-Kwok, I., et al. (2008). Bypassing cellular EGF receptor dependence through epithelial-to-mesenchymal-like transitions. Clinical & Experimental Metastasis, 25(6), 685–693. doi:10.​1007/​s10585-007-9121-7.
11.
go back to reference Lo, H. W., Hsu, S. C., Xia, W., Cao, X., Shih, J. Y., Wei, Y., et al. (2007). Epidermal growth factor receptor cooperates with signal transducer and activator of transcription 3 to induce epithelial–mesenchymal transition in cancer cells via up-regulation of TWIST gene expression. Cancer Research, 67(19), 9066–9076. doi:10.1158/0008-5472.CAN-07-0575.PubMed Lo, H. W., Hsu, S. C., Xia, W., Cao, X., Shih, J. Y., Wei, Y., et al. (2007). Epidermal growth factor receptor cooperates with signal transducer and activator of transcription 3 to induce epithelial–mesenchymal transition in cancer cells via up-regulation of TWIST gene expression. Cancer Research, 67(19), 9066–9076. doi:10.​1158/​0008-5472.​CAN-07-0575.PubMed
12.
go back to reference Birchmeier, C., Birchmeier, W., Gherardi, E., & Vande Woude, G. F. (2003). Met, metastasis, motility and more. Nature Reviews Molecular Cell Biology, 4(12), 915–925. doi:10.1038/nrm1261nrm1261.PubMed Birchmeier, C., Birchmeier, W., Gherardi, E., & Vande Woude, G. F. (2003). Met, metastasis, motility and more. Nature Reviews Molecular Cell Biology, 4(12), 915–925. doi:10.​1038/​nrm1261nrm1261.PubMed
13.
go back to reference Boyer, B., & Thiery, J. P. (1993). Cyclic AMP distinguishes between two functions of acidic FGF in a rat bladder carcinoma cell line. The Journal of Cell Biology, 120(3), 767–776.PubMed Boyer, B., & Thiery, J. P. (1993). Cyclic AMP distinguishes between two functions of acidic FGF in a rat bladder carcinoma cell line. The Journal of Cell Biology, 120(3), 767–776.PubMed
14.
go back to reference Savagner, P., Yamada, K. M., & Thiery, J. P. (1997). The zinc-finger protein slug causes desmosome dissociation, an initial and necessary step for growth factor-induced epithelial–mesenchymal transition. The Journal of Cell Biology, 137(6), 1403–1419.PubMed Savagner, P., Yamada, K. M., & Thiery, J. P. (1997). The zinc-finger protein slug causes desmosome dissociation, an initial and necessary step for growth factor-induced epithelial–mesenchymal transition. The Journal of Cell Biology, 137(6), 1403–1419.PubMed
15.
go back to reference Bellusci, S., Moens, G., Thiery, J. P., & Jouanneau, J. (1994). A scatter factor-like factor is produced by a metastatic variant of a rat bladder carcinoma cell line. Journal of Cell Science, 107(Pt 5), 1277–1287.PubMed Bellusci, S., Moens, G., Thiery, J. P., & Jouanneau, J. (1994). A scatter factor-like factor is produced by a metastatic variant of a rat bladder carcinoma cell line. Journal of Cell Science, 107(Pt 5), 1277–1287.PubMed
16.
go back to reference Grotegut, S., von Schweinitz, D., Christofori, G., & Lehembre, F. (2006). Hepatocyte growth factor induces cell scattering through MAPK/Egr-1-mediated upregulation of Snail. EMBO Journal, 25(15), 3534–3545. doi:10.1038/sj.emboj.7601213.PubMed Grotegut, S., von Schweinitz, D., Christofori, G., & Lehembre, F. (2006). Hepatocyte growth factor induces cell scattering through MAPK/Egr-1-mediated upregulation of Snail. EMBO Journal, 25(15), 3534–3545. doi:10.​1038/​sj.​emboj.​7601213.PubMed
17.
go back to reference Min, C., Eddy, S. F., Sherr, D. H., & Sonenshein, G. E. (2008). NF-kappaB and epithelial to mesenchymal transition of cancer. Journal of Cellular Biochemistry, 104(3), 733–744. doi:10.1002/jcb.21695.PubMed Min, C., Eddy, S. F., Sherr, D. H., & Sonenshein, G. E. (2008). NF-kappaB and epithelial to mesenchymal transition of cancer. Journal of Cellular Biochemistry, 104(3), 733–744. doi:10.​1002/​jcb.​21695.PubMed
18.
go back to reference Taylor, M. A., Parvani, J. G., & Schiemann, W. P. (2010). The pathophysiology of epithelial–mesenchymal transition induced by transforming growth factor-beta in normal and malignant mammary epithelial cells. Journal of Mammary Gland Biology and Neoplasia, 15(2), 169–190. doi:10.1007/s10911-010-9181-1.PubMed Taylor, M. A., Parvani, J. G., & Schiemann, W. P. (2010). The pathophysiology of epithelial–mesenchymal transition induced by transforming growth factor-beta in normal and malignant mammary epithelial cells. Journal of Mammary Gland Biology and Neoplasia, 15(2), 169–190. doi:10.​1007/​s10911-010-9181-1.PubMed
19.
go back to reference Vincan, E., & Barker, N. (2008). The upstream components of the Wnt signalling pathway in the dynamic EMT and MET associated with colorectal cancer progression. Clinical & Experimental Metastasis, 25(6), 657–663. doi:10.1007/s10585-008-9156-4. Vincan, E., & Barker, N. (2008). The upstream components of the Wnt signalling pathway in the dynamic EMT and MET associated with colorectal cancer progression. Clinical & Experimental Metastasis, 25(6), 657–663. doi:10.​1007/​s10585-008-9156-4.
20.
go back to reference Wang, Z., Li, Y., Kong, D., & Sarkar, F. H. (2010). The role of Notch signaling pathway in epithelial–mesenchymal transition (EMT) during development and tumor aggressiveness. Current Drug Targets, 11(6), 745–751.PubMed Wang, Z., Li, Y., Kong, D., & Sarkar, F. H. (2010). The role of Notch signaling pathway in epithelial–mesenchymal transition (EMT) during development and tumor aggressiveness. Current Drug Targets, 11(6), 745–751.PubMed
21.
go back to reference Wendt, M. K., Allington, T. M., & Schiemann, W. P. (2009). Mechanisms of the epithelial–mesenchymal transition by TGF-beta. Future Oncology, 5(8), 1145–1168. doi:10.2217/fon.09.90.PubMed Wendt, M. K., Allington, T. M., & Schiemann, W. P. (2009). Mechanisms of the epithelial–mesenchymal transition by TGF-beta. Future Oncology, 5(8), 1145–1168. doi:10.​2217/​fon.​09.​90.PubMed
23.
go back to reference Tian, F., DaCosta Byfield, S., Parks, W. T., Yoo, S., Felici, A., Tang, B., et al. (2003). Reduction in Smad2/3 signaling enhances tumorigenesis but suppresses metastasis of breast cancer cell lines. Cancer Research, 63(23), 8284–8292.PubMed Tian, F., DaCosta Byfield, S., Parks, W. T., Yoo, S., Felici, A., Tang, B., et al. (2003). Reduction in Smad2/3 signaling enhances tumorigenesis but suppresses metastasis of breast cancer cell lines. Cancer Research, 63(23), 8284–8292.PubMed
24.
go back to reference Tian, F., Byfield, S. D., Parks, W. T., Stuelten, C. H., Nemani, D., Zhang, Y. E., et al. (2004). Smad-binding defective mutant of transforming growth factor beta type I receptor enhances tumorigenesis but suppresses metastasis of breast cancer cell lines. Cancer Research, 64(13), 4523–4530. doi:10.1158/0008-5472.CAN-04-003064/13/4523.PubMed Tian, F., Byfield, S. D., Parks, W. T., Stuelten, C. H., Nemani, D., Zhang, Y. E., et al. (2004). Smad-binding defective mutant of transforming growth factor beta type I receptor enhances tumorigenesis but suppresses metastasis of breast cancer cell lines. Cancer Research, 64(13), 4523–4530. doi:10.​1158/​0008-5472.​CAN-04-003064/​13/​4523.PubMed
25.
go back to reference Deckers, M., van Dinther, M., Buijs, J., Que, I., Lowik, C., van der Pluijm, G., et al. (2006). The tumor suppressor Smad4 is required for transforming growth factor beta-induced epithelial to mesenchymal transition and bone metastasis of breast cancer cells. Cancer Research, 66(4), 2202–2209. doi:10.1158/0008-5472.CAN-05-3560.PubMed Deckers, M., van Dinther, M., Buijs, J., Que, I., Lowik, C., van der Pluijm, G., et al. (2006). The tumor suppressor Smad4 is required for transforming growth factor beta-induced epithelial to mesenchymal transition and bone metastasis of breast cancer cells. Cancer Research, 66(4), 2202–2209. doi:10.​1158/​0008-5472.​CAN-05-3560.PubMed
26.
go back to reference Kang, Y., He, W., Tulley, S., Gupta, G. P., Serganova, I., Chen, C. R., et al. (2005). Breast cancer bone metastasis mediated by the Smad tumor suppressor pathway. Proceedings of the National Academy of Sciences of the United States of America, 102(39), 13909–13914. doi:10.1073/pnas.0506517102.PubMed Kang, Y., He, W., Tulley, S., Gupta, G. P., Serganova, I., Chen, C. R., et al. (2005). Breast cancer bone metastasis mediated by the Smad tumor suppressor pathway. Proceedings of the National Academy of Sciences of the United States of America, 102(39), 13909–13914. doi:10.​1073/​pnas.​0506517102.PubMed
27.
go back to reference Hayashi, H., Abdollah, S., Qiu, Y., Cai, J., Xu, Y. Y., Grinnell, B. W., et al. (1997). The MAD-related protein Smad7 associates with the TGFbeta receptor and functions as an antagonist of TGFbeta signaling. Cell, 89(7), 1165–1173.PubMed Hayashi, H., Abdollah, S., Qiu, Y., Cai, J., Xu, Y. Y., Grinnell, B. W., et al. (1997). The MAD-related protein Smad7 associates with the TGFbeta receptor and functions as an antagonist of TGFbeta signaling. Cell, 89(7), 1165–1173.PubMed
28.
go back to reference Souchelnytskyi, S., Nakayama, T., Nakao, A., Moren, A., Heldin, C. H., Christian, J. L., et al. (1998). Physical and functional interaction of murine and Xenopus Smad7 with bone morphogenetic protein receptors and transforming growth factor-beta receptors. Journal of Biological Chemistry, 273(39), 25364–25370.PubMed Souchelnytskyi, S., Nakayama, T., Nakao, A., Moren, A., Heldin, C. H., Christian, J. L., et al. (1998). Physical and functional interaction of murine and Xenopus Smad7 with bone morphogenetic protein receptors and transforming growth factor-beta receptors. Journal of Biological Chemistry, 273(39), 25364–25370.PubMed
29.
go back to reference Azuma, H., Ehata, S., Miyazaki, H., Watabe, T., Maruyama, O., Imamura, T., et al. (2005). Effect of Smad7 expression on metastasis of mouse mammary carcinoma JygMC(A) cells. Journal of the National Cancer Institute, 97(23), 1734–1746. doi:10.1093/jnci/dji399.PubMed Azuma, H., Ehata, S., Miyazaki, H., Watabe, T., Maruyama, O., Imamura, T., et al. (2005). Effect of Smad7 expression on metastasis of mouse mammary carcinoma JygMC(A) cells. Journal of the National Cancer Institute, 97(23), 1734–1746. doi:10.​1093/​jnci/​dji399.PubMed
30.
go back to reference Leivonen, S. K., Ala-Aho, R., Koli, K., Grenman, R., Peltonen, J., & Kahari, V. M. (2006). Activation of Smad signaling enhances collagenase-3 (MMP-13) expression and invasion of head and neck squamous carcinoma cells. Oncogene, 25(18), 2588–2600. doi:10.1038/sj.Onc.1209291.PubMed Leivonen, S. K., Ala-Aho, R., Koli, K., Grenman, R., Peltonen, J., & Kahari, V. M. (2006). Activation of Smad signaling enhances collagenase-3 (MMP-13) expression and invasion of head and neck squamous carcinoma cells. Oncogene, 25(18), 2588–2600. doi:10.​1038/​sj.​Onc.​1209291.PubMed
31.
go back to reference Leivonen, S. K., & Kahari, V. M. (2007). Transforming growth factor-beta signaling in cancer invasion and metastasis. International Journal of Cancer, 121(10), 2119–2124. doi:10.1002/ijc.23113. Leivonen, S. K., & Kahari, V. M. (2007). Transforming growth factor-beta signaling in cancer invasion and metastasis. International Journal of Cancer, 121(10), 2119–2124. doi:10.​1002/​ijc.​23113.
32.
go back to reference Javelaud, D., Mohammad, K. S., McKenna, C. R., Fournier, P., Luciani, F., Niewolna, M., et al. (2007). Stable overexpression of Smad7 in human melanoma cells impairs bone metastasis. Cancer Research, 67(5), 2317–2324. doi:10.1158/0008-5472.CAN-06-3950.PubMed Javelaud, D., Mohammad, K. S., McKenna, C. R., Fournier, P., Luciani, F., Niewolna, M., et al. (2007). Stable overexpression of Smad7 in human melanoma cells impairs bone metastasis. Cancer Research, 67(5), 2317–2324. doi:10.​1158/​0008-5472.​CAN-06-3950.PubMed
33.
go back to reference Janda, E., Lehmann, K., Killisch, I., Jechlinger, M., Herzig, M., Downward, J., et al. (2002). Ras and TGF[beta] cooperatively regulate epithelial cell plasticity and metastasis: dissection of Ras signaling pathways. The Journal of Cell Biology, 156(2), 299–313. doi:10.1083/jcb.200109037jcb.200109037.PubMed Janda, E., Lehmann, K., Killisch, I., Jechlinger, M., Herzig, M., Downward, J., et al. (2002). Ras and TGF[beta] cooperatively regulate epithelial cell plasticity and metastasis: dissection of Ras signaling pathways. The Journal of Cell Biology, 156(2), 299–313. doi:10.​1083/​jcb.​200109037jcb.​200109037.PubMed
34.
go back to reference Xie, L., Law, B. K., Chytil, A. M., Brown, K. A., Aakre, M. E., & Moses, H. L. (2004). Activation of the Erk pathway is required for TGF-beta1-induced EMT in vitro. Neoplasia, 6(5), 603–610. doi:10.1593/neo.04241.PubMed Xie, L., Law, B. K., Chytil, A. M., Brown, K. A., Aakre, M. E., & Moses, H. L. (2004). Activation of the Erk pathway is required for TGF-beta1-induced EMT in vitro. Neoplasia, 6(5), 603–610. doi:10.​1593/​neo.​04241.PubMed
35.
go back to reference Neil, J. R., Johnson, K. M., Nemenoff, R. A., & Schiemann, W. P. (2008). Cox-2 inactivates Smad signaling and enhances EMT stimulated by TGF-beta through a PGE2-dependent mechanisms. Carcinogenesis, 29(11), 2227–2235. doi:10.1093/carcin/bgn202.PubMed Neil, J. R., Johnson, K. M., Nemenoff, R. A., & Schiemann, W. P. (2008). Cox-2 inactivates Smad signaling and enhances EMT stimulated by TGF-beta through a PGE2-dependent mechanisms. Carcinogenesis, 29(11), 2227–2235. doi:10.​1093/​carcin/​bgn202.PubMed
36.
go back to reference Bhowmick, N. A., Zent, R., Ghiassi, M., McDonnell, M., & Moses, H. L. (2001). Integrin beta 1 signaling is necessary for transforming growth factor-beta activation of p38MAPK and epithelial plasticity. Journal of Biological Chemistry, 276(50), 46707–46713. doi:10.1074/jbc.M106176200M106176200.PubMed Bhowmick, N. A., Zent, R., Ghiassi, M., McDonnell, M., & Moses, H. L. (2001). Integrin beta 1 signaling is necessary for transforming growth factor-beta activation of p38MAPK and epithelial plasticity. Journal of Biological Chemistry, 276(50), 46707–46713. doi:10.​1074/​jbc.​M106176200M10617​6200.PubMed
37.
go back to reference Galliher, A. J., & Schiemann, W. P. (2006). Beta3 integrin and Src facilitate transforming growth factor-beta mediated induction of epithelial–mesenchymal transition in mammary epithelial cells. Breast Cancer Research, 8(4), R42. doi:10.1186/bcr1524.PubMed Galliher, A. J., & Schiemann, W. P. (2006). Beta3 integrin and Src facilitate transforming growth factor-beta mediated induction of epithelial–mesenchymal transition in mammary epithelial cells. Breast Cancer Research, 8(4), R42. doi:10.​1186/​bcr1524.PubMed
38.
go back to reference Galliher-Beckley, A. J., & Schiemann, W. P. (2008). Grb2 binding to Tyr284 in TbetaR-II is essential for mammary tumor growth and metastasis stimulated by TGF-beta. Carcinogenesis, 29(2), 244–251. doi:10.1093/carcin/bgm245.PubMed Galliher-Beckley, A. J., & Schiemann, W. P. (2008). Grb2 binding to Tyr284 in TbetaR-II is essential for mammary tumor growth and metastasis stimulated by TGF-beta. Carcinogenesis, 29(2), 244–251. doi:10.​1093/​carcin/​bgm245.PubMed
40.
go back to reference Miele, L., & Osborne, B. (1999). Arbiter of differentiation and death: Notch signaling meets apoptosis. Journal of Cellular Physiology, 181(3), 393–409. doi:10.1002/(SICI)1097-4652(199912)181:3<393::AID-JCP3>3.0.CO;2-6 [pii]10.1002/(SICI)1097-4652(199912)181:3<393::AID-JCP3>3.0.CO;2-6.PubMed Miele, L., & Osborne, B. (1999). Arbiter of differentiation and death: Notch signaling meets apoptosis. Journal of Cellular Physiology, 181(3), 393–409. doi:10.1002/(SICI)1097-4652(199912)181:3<393::AID-JCP3>3.0.CO;2-6 [pii]10.1002/(SICI)1097-4652(199912)181:3<393::AID-JCP3>3.0.CO;2-6.PubMed
41.
go back to reference Niessen, K., Fu, Y., Chang, L., Hoodless, P. A., McFadden, D., & Karsan, A. (2008). Slug is a direct Notch target required for initiation of cardiac cushion cellularization. The Journal of Cell Biology, 182(2), 315–325. doi:10.1083/jcb.200710067.PubMed Niessen, K., Fu, Y., Chang, L., Hoodless, P. A., McFadden, D., & Karsan, A. (2008). Slug is a direct Notch target required for initiation of cardiac cushion cellularization. The Journal of Cell Biology, 182(2), 315–325. doi:10.​1083/​jcb.​200710067.PubMed
42.
43.
go back to reference Niimi, H., Pardali, K., Vanlandewijck, M., Heldin, C. H., & Moustakas, A. (2007). Notch signaling is necessary for epithelial growth arrest by TGF-beta. The Journal of Cell Biology, 176(5), 695–707. doi:10.1083/jcb.200612129.PubMed Niimi, H., Pardali, K., Vanlandewijck, M., Heldin, C. H., & Moustakas, A. (2007). Notch signaling is necessary for epithelial growth arrest by TGF-beta. The Journal of Cell Biology, 176(5), 695–707. doi:10.​1083/​jcb.​200612129.PubMed
44.
go back to reference Jechlinger, M., Sommer, A., Moriggl, R., Seither, P., Kraut, N., Capodiecci, P., et al. (2006). Autocrine PDGFR signaling promotes mammary cancer metastasis. The Journal of Clinical Investigation, 116(6), 1561–1570. doi:10.1172/JCI24652.PubMed Jechlinger, M., Sommer, A., Moriggl, R., Seither, P., Kraut, N., Capodiecci, P., et al. (2006). Autocrine PDGFR signaling promotes mammary cancer metastasis. The Journal of Clinical Investigation, 116(6), 1561–1570. doi:10.​1172/​JCI24652.PubMed
45.
go back to reference Fischer, A. N., Fuchs, E., Mikula, M., Huber, H., Beug, H., & Mikulits, W. (2007). PDGF essentially links TGF-beta signaling to nuclear beta-catenin accumulation in hepatocellular carcinoma progression. Oncogene, 26(23), 3395–3405. doi:10.1038/sj.onc.1210121.PubMed Fischer, A. N., Fuchs, E., Mikula, M., Huber, H., Beug, H., & Mikulits, W. (2007). PDGF essentially links TGF-beta signaling to nuclear beta-catenin accumulation in hepatocellular carcinoma progression. Oncogene, 26(23), 3395–3405. doi:10.​1038/​sj.​onc.​1210121.PubMed
46.
go back to reference Gotzmann, J., Fischer, A. N., Zojer, M., Mikula, M., Proell, V., Huber, H., et al. (2006). A crucial function of PDGF in TGF-beta-mediated cancer progression of hepatocytes. Oncogene, 25(22), 3170–3185. doi:10.1038/sj.onc.1209083.PubMed Gotzmann, J., Fischer, A. N., Zojer, M., Mikula, M., Proell, V., Huber, H., et al. (2006). A crucial function of PDGF in TGF-beta-mediated cancer progression of hepatocytes. Oncogene, 25(22), 3170–3185. doi:10.​1038/​sj.​onc.​1209083.PubMed
47.
go back to reference Zhao, J. H., Luo, Y., Jiang, Y. G., He, D. L., & Wu, C. T. (2011). Knockdown of beta-catenin through shRNA cause a reversal of EMT and metastatic phenotypes induced by HIF-1alpha. Cancer Investigation, 29(6), 377–382. doi:10.3109/07357907.2010.512595.PubMed Zhao, J. H., Luo, Y., Jiang, Y. G., He, D. L., & Wu, C. T. (2011). Knockdown of beta-catenin through shRNA cause a reversal of EMT and metastatic phenotypes induced by HIF-1alpha. Cancer Investigation, 29(6), 377–382. doi:10.​3109/​07357907.​2010.​512595.PubMed
48.
go back to reference Cheng, Z. X., Sun, B., Wang, S. J., Gao, Y., Zhang, Y. M., Zhou, H. X., et al. (2011). Nuclear factor-kappaB-dependent epithelial to mesenchymal transition induced by HIF-1alpha activation in pancreatic cancer cells under hypoxic conditions. PLoS One, 6(8), e23752. doi:10.1371/journal.pone.0023752PONE-D-11-07211.PubMed Cheng, Z. X., Sun, B., Wang, S. J., Gao, Y., Zhang, Y. M., Zhou, H. X., et al. (2011). Nuclear factor-kappaB-dependent epithelial to mesenchymal transition induced by HIF-1alpha activation in pancreatic cancer cells under hypoxic conditions. PLoS One, 6(8), e23752. doi:10.​1371/​journal.​pone.​0023752PONE-D-11-07211.PubMed
49.
go back to reference Batlle, E., Sancho, E., Franci, C., Dominguez, D., Monfar, M., Baulida, J., et al. (2000). The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nature Cell Biology, 2(2), 84–89. doi:10.1038/35000034.PubMed Batlle, E., Sancho, E., Franci, C., Dominguez, D., Monfar, M., Baulida, J., et al. (2000). The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nature Cell Biology, 2(2), 84–89. doi:10.​1038/​35000034.PubMed
50.
go back to reference Cano, A., Perez-Moreno, M. A., Rodrigo, I., Locascio, A., Blanco, M. J., del Barrio, M. G., et al. (2000). The transcription factor snail controls epithelial–mesenchymal transitions by repressing E-cadherin expression. Nature Cell Biology, 2(2), 76–83. doi:10.1038/35000025.PubMed Cano, A., Perez-Moreno, M. A., Rodrigo, I., Locascio, A., Blanco, M. J., del Barrio, M. G., et al. (2000). The transcription factor snail controls epithelial–mesenchymal transitions by repressing E-cadherin expression. Nature Cell Biology, 2(2), 76–83. doi:10.​1038/​35000025.PubMed
51.
go back to reference Hajra, K. M., Chen, D. Y., & Fearon, E. R. (2002). The SLUG zinc-finger protein represses E-cadherin in breast cancer. Cancer Research, 62(6), 1613–1618.PubMed Hajra, K. M., Chen, D. Y., & Fearon, E. R. (2002). The SLUG zinc-finger protein represses E-cadherin in breast cancer. Cancer Research, 62(6), 1613–1618.PubMed
52.
go back to reference Comijn, J., Berx, G., Vermassen, P., Verschueren, K., van Grunsven, L., Bruyneel, E., et al. (2001). The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion. Molecular Cell, 7(6), 1267–1278. doi:S1097-2765(01)00260-X.PubMed Comijn, J., Berx, G., Vermassen, P., Verschueren, K., van Grunsven, L., Bruyneel, E., et al. (2001). The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion. Molecular Cell, 7(6), 1267–1278. doi:S1097-2765(01)00260-X.PubMed
53.
go back to reference Eger, A., Aigner, K., Sonderegger, S., Dampier, B., Oehler, S., Schreiber, M., et al. (2005). DeltaEF1 is a transcriptional repressor of E-cadherin and regulates epithelial plasticity in breast cancer cells. Oncogene, 24(14), 2375–2385. doi:10.1038/sj.onc.1208429.PubMed Eger, A., Aigner, K., Sonderegger, S., Dampier, B., Oehler, S., Schreiber, M., et al. (2005). DeltaEF1 is a transcriptional repressor of E-cadherin and regulates epithelial plasticity in breast cancer cells. Oncogene, 24(14), 2375–2385. doi:10.​1038/​sj.​onc.​1208429.PubMed
54.
go back to reference Remacle, J. E., Kraft, H., Lerchner, W., Wuytens, G., Collart, C., Verschueren, K., et al. (1999). New mode of DNA binding of multi-zinc finger transcription factors: deltaEF1 family members bind with two hands to two target sites. EMBO Journal, 18(18), 5073–5084. doi:10.1093/emboj/18.18.5073.PubMed Remacle, J. E., Kraft, H., Lerchner, W., Wuytens, G., Collart, C., Verschueren, K., et al. (1999). New mode of DNA binding of multi-zinc finger transcription factors: deltaEF1 family members bind with two hands to two target sites. EMBO Journal, 18(18), 5073–5084. doi:10.​1093/​emboj/​18.​18.​5073.PubMed
56.
go back to reference Katoh, M. (2004). Human FOX gene family (review). International Journal of Oncology, 25(5), 1495–1500.PubMed Katoh, M. (2004). Human FOX gene family (review). International Journal of Oncology, 25(5), 1495–1500.PubMed
57.
go back to reference Mani, S. A., Yang, J., Brooks, M., Schwaninger, G., Zhou, A., Miura, N., et al. (2007). Mesenchyme Forkhead 1 (FOXC2) plays a key role in metastasis and is associated with aggressive basal-like breast cancers. Proceedings of the National Academy of Sciences of the United States of America, 104(24), 10069–10074. doi:10.1073/pnas.0703900104.PubMed Mani, S. A., Yang, J., Brooks, M., Schwaninger, G., Zhou, A., Miura, N., et al. (2007). Mesenchyme Forkhead 1 (FOXC2) plays a key role in metastasis and is associated with aggressive basal-like breast cancers. Proceedings of the National Academy of Sciences of the United States of America, 104(24), 10069–10074. doi:10.​1073/​pnas.​0703900104.PubMed
58.
go back to reference Bloushtain-Qimron, N., Yao, J., Snyder, E. L., Shipitsin, M., Campbell, L. L., Mani, S. A., et al. (2008). Cell type-specific DNA methylation patterns in the human breast. Proceedings of the National Academy of Sciences of the United States of America, 105(37), 14076–14081. doi:10.1073/pnas.0805206105.PubMed Bloushtain-Qimron, N., Yao, J., Snyder, E. L., Shipitsin, M., Campbell, L. L., Mani, S. A., et al. (2008). Cell type-specific DNA methylation patterns in the human breast. Proceedings of the National Academy of Sciences of the United States of America, 105(37), 14076–14081. doi:10.​1073/​pnas.​0805206105.PubMed
59.
go back to reference Ray, P. S., Wang, J., Qu, Y., Sim, M. S., Shamonki, J., Bagaria, S. P., et al. (2010). FOXC1 is a potential prognostic biomarker with functional significance in basal-like breast cancer. Cancer Research, 70(10), 3870–3876. doi:10.1158/0008-5472.CAN-09-4120.PubMed Ray, P. S., Wang, J., Qu, Y., Sim, M. S., Shamonki, J., Bagaria, S. P., et al. (2010). FOXC1 is a potential prognostic biomarker with functional significance in basal-like breast cancer. Cancer Research, 70(10), 3870–3876. doi:10.​1158/​0008-5472.​CAN-09-4120.PubMed
60.
go back to reference Feuerborn, A., Srivastava, P. K., Kuffer, S., Grandy, W. A., Sijmonsma, T. P., Gretz, N., et al. (2011). The Forkhead factor FoxQ1 influences epithelial differentiation. Journal of Cellular Physiology, 226(3), 710–719. doi:10.1002/jcp. 22385.PubMed Feuerborn, A., Srivastava, P. K., Kuffer, S., Grandy, W. A., Sijmonsma, T. P., Gretz, N., et al. (2011). The Forkhead factor FoxQ1 influences epithelial differentiation. Journal of Cellular Physiology, 226(3), 710–719. doi:10.​1002/​jcp.​ 22385.PubMed
61.
62.
go back to reference Zhang, H., Meng, F., Liu, G., Zhang, B., Zhu, J., Wu, F., et al. (2011). Forkhead transcription factor foxq1 promotes epithelial–mesenchymal transition and breast cancer metastasis. Cancer Research, 71(4), 1292–1301. doi:10.1158/0008-5472.CAN-10-2825.PubMed Zhang, H., Meng, F., Liu, G., Zhang, B., Zhu, J., Wu, F., et al. (2011). Forkhead transcription factor foxq1 promotes epithelial–mesenchymal transition and breast cancer metastasis. Cancer Research, 71(4), 1292–1301. doi:10.​1158/​0008-5472.​CAN-10-2825.PubMed
63.
go back to reference Tang, Y., Shu, G., Yuan, X., Jing, N., & Song, J. (2011). FOXA2 functions as a suppressor of tumor metastasis by inhibition of epithelial-to-mesenchymal transition in human lung cancers. Cell Research, 21(2), 316–326. doi:10.1038/cr.2010.126.PubMed Tang, Y., Shu, G., Yuan, X., Jing, N., & Song, J. (2011). FOXA2 functions as a suppressor of tumor metastasis by inhibition of epithelial-to-mesenchymal transition in human lung cancers. Cell Research, 21(2), 316–326. doi:10.​1038/​cr.​2010.​126.PubMed
64.
go back to reference Yori, J. L., Johnson, E., Zhou, G., Jain, M. K., & Keri, R. A. (2010). Kruppel-like factor 4 inhibits epithelial-to-mesenchymal transition through regulation of E-cadherin gene expression. Journal of Biological Chemistry, 285(22), 16854–16863. doi:10.1074/jbc.M110.114546.PubMed Yori, J. L., Johnson, E., Zhou, G., Jain, M. K., & Keri, R. A. (2010). Kruppel-like factor 4 inhibits epithelial-to-mesenchymal transition through regulation of E-cadherin gene expression. Journal of Biological Chemistry, 285(22), 16854–16863. doi:10.​1074/​jbc.​M110.​114546.PubMed
65.
go back to reference Gumireddy, K., Li, A., Gimotty, P. A., Klein-Szanto, A. J., Showe, L. C., Katsaros, D., et al. (2009). KLF17 is a negative regulator of epithelial–mesenchymal transition and metastasis in breast cancer. Nature Cell Biology, 11(11), 1297–1304. doi:10.1038/ncb1974.PubMed Gumireddy, K., Li, A., Gimotty, P. A., Klein-Szanto, A. J., Showe, L. C., Katsaros, D., et al. (2009). KLF17 is a negative regulator of epithelial–mesenchymal transition and metastasis in breast cancer. Nature Cell Biology, 11(11), 1297–1304. doi:10.​1038/​ncb1974.PubMed
66.
go back to reference Wang, X., Zheng, M., Liu, G., Xia, W., McKeown-Longo, P. J., Hung, M. C., et al. (2007). Kruppel-like factor 8 induces epithelial to mesenchymal transition and epithelial cell invasion. Cancer Research, 67(15), 7184–7193. doi:10.1158/0008-5472.CAN-06-4729.PubMed Wang, X., Zheng, M., Liu, G., Xia, W., McKeown-Longo, P. J., Hung, M. C., et al. (2007). Kruppel-like factor 8 induces epithelial to mesenchymal transition and epithelial cell invasion. Cancer Research, 67(15), 7184–7193. doi:10.​1158/​0008-5472.​CAN-06-4729.PubMed
67.
go back to reference Holian, J., Qi, W., Kelly, D. J., Zhang, Y., Mreich, E., Pollock, C. A., et al. (2008). Role of Kruppel-like factor 6 in transforming growth factor-beta1-induced epithelial–mesenchymal transition of proximal tubule cells. American Journal of Physiology. Renal Physiology, 295(5), F1388–F1396. doi:10.1152/ajprenal.00055.2008.PubMed Holian, J., Qi, W., Kelly, D. J., Zhang, Y., Mreich, E., Pollock, C. A., et al. (2008). Role of Kruppel-like factor 6 in transforming growth factor-beta1-induced epithelial–mesenchymal transition of proximal tubule cells. American Journal of Physiology. Renal Physiology, 295(5), F1388–F1396. doi:10.​1152/​ajprenal.​00055.​2008.PubMed
68.
go back to reference Yu, M., Smolen, G. A., Zhang, J., Wittner, B., Schott, B. J., Brachtel, E., et al. (2009). A developmentally regulated inducer of EMT, LBX1, contributes to breast cancer progression. Genes & Development, 23(15), 1737–1742. doi:10.1101/gad.1809309. Yu, M., Smolen, G. A., Zhang, J., Wittner, B., Schott, B. J., Brachtel, E., et al. (2009). A developmentally regulated inducer of EMT, LBX1, contributes to breast cancer progression. Genes & Development, 23(15), 1737–1742. doi:10.​1101/​gad.​1809309.
69.
go back to reference Evdokimova, V., Tognon, C., Ng, T., Ruzanov, P., Melnyk, N., Fink, D., et al. (2009). Translational activation of snail1 and other developmentally regulated transcription factors by YB-1 promotes an epithelial–mesenchymal transition. Cancer Cell, 15(5), 402–415. doi:10.1016/j.ccr.2009.03.017.PubMed Evdokimova, V., Tognon, C., Ng, T., Ruzanov, P., Melnyk, N., Fink, D., et al. (2009). Translational activation of snail1 and other developmentally regulated transcription factors by YB-1 promotes an epithelial–mesenchymal transition. Cancer Cell, 15(5), 402–415. doi:10.​1016/​j.​ccr.​2009.​03.​017.PubMed
70.
go back to reference Fernando, R. I., Litzinger, M., Trono, P., Hamilton, D. H., Schlom, J., & Palena, C. (2010). The T-box transcription factor Brachyury promotes epithelial–mesenchymal transition in human tumor cells. The Journal of Clinical Investigation, 120(2), 533–544. doi:10.1172/JCI38379.PubMed Fernando, R. I., Litzinger, M., Trono, P., Hamilton, D. H., Schlom, J., & Palena, C. (2010). The T-box transcription factor Brachyury promotes epithelial–mesenchymal transition in human tumor cells. The Journal of Clinical Investigation, 120(2), 533–544. doi:10.​1172/​JCI38379.PubMed
71.
go back to reference Beltran, M., Puig, I., Pena, C., Garcia, J. M., Alvarez, A. B., Pena, R., et al. (2008). A natural antisense transcript regulates Zeb2/Sip1 gene expression during Snail1-induced epithelial–mesenchymal transition. Genes & Development, 22(6), 756–769. doi:10.1101/gad.455708. Beltran, M., Puig, I., Pena, C., Garcia, J. M., Alvarez, A. B., Pena, R., et al. (2008). A natural antisense transcript regulates Zeb2/Sip1 gene expression during Snail1-induced epithelial–mesenchymal transition. Genes & Development, 22(6), 756–769. doi:10.​1101/​gad.​455708.
73.
go back to reference Gregory, P. A., Bert, A. G., Paterson, E. L., Barry, S. C., Tsykin, A., Farshid, G., et al. (2008). The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nature Cell Biology, 10(5), 593–601. doi:10.1038/ncb1722.PubMed Gregory, P. A., Bert, A. G., Paterson, E. L., Barry, S. C., Tsykin, A., Farshid, G., et al. (2008). The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nature Cell Biology, 10(5), 593–601. doi:10.​1038/​ncb1722.PubMed
74.
go back to reference Gregory, P. A., Bracken, C. P., Bert, A. G., & Goodall, G. J. (2008). MicroRNAs as regulators of epithelial–mesenchymal transition. Cell Cycle, 7(20), 3112–3118.PubMed Gregory, P. A., Bracken, C. P., Bert, A. G., & Goodall, G. J. (2008). MicroRNAs as regulators of epithelial–mesenchymal transition. Cell Cycle, 7(20), 3112–3118.PubMed
75.
go back to reference Park, S. M., Gaur, A. B., Lengyel, E., & Peter, M. E. (2008). The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes & Development, 22(7), 894–907. doi:10.1101/gad.1640608. Park, S. M., Gaur, A. B., Lengyel, E., & Peter, M. E. (2008). The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes & Development, 22(7), 894–907. doi:10.​1101/​gad.​1640608.
76.
go back to reference Gebeshuber, C. A., Zatloukal, K., & Martinez, J. (2009). miR-29a suppresses tristetraprolin, which is a regulator of epithelial polarity and metastasis. EMBO Reports, 10(4), 400–405. doi:10.1038/embor.2009.9.PubMed Gebeshuber, C. A., Zatloukal, K., & Martinez, J. (2009). miR-29a suppresses tristetraprolin, which is a regulator of epithelial polarity and metastasis. EMBO Reports, 10(4), 400–405. doi:10.​1038/​embor.​2009.​9.PubMed
77.
go back to reference Kong, W., Yang, H., He, L., Zhao, J. J., Coppola, D., Dalton, W. S., et al. (2008). MicroRNA-155 is regulated by the transforming growth factor beta/Smad pathway and contributes to epithelial cell plasticity by targeting RhoA. Molecular and Cellular Biology, 28(22), 6773–6784. doi:10.1128/MCB.00941-08.PubMed Kong, W., Yang, H., He, L., Zhao, J. J., Coppola, D., Dalton, W. S., et al. (2008). MicroRNA-155 is regulated by the transforming growth factor beta/Smad pathway and contributes to epithelial cell plasticity by targeting RhoA. Molecular and Cellular Biology, 28(22), 6773–6784. doi:10.​1128/​MCB.​00941-08.PubMed
78.
go back to reference Dong, P., Kaneuchi, M., Watari, H., Hamada, J., Sudo, S., Ju, J., et al. (2011). MicroRNA-194 inhibits epithelial to mesenchymal transition of endometrial cancer cells by targeting oncogene BMI-1. Molecular Cancer, 10, 99. doi:10.1186/1476-4598-10-99.PubMed Dong, P., Kaneuchi, M., Watari, H., Hamada, J., Sudo, S., Ju, J., et al. (2011). MicroRNA-194 inhibits epithelial to mesenchymal transition of endometrial cancer cells by targeting oncogene BMI-1. Molecular Cancer, 10, 99. doi:10.​1186/​1476-4598-10-99.PubMed
79.
go back to reference Kumarswamy, R., Mudduluru, G., Ceppi, P., Muppala, S., Kozlowski, M., Niklinski, J., et al. (2012). MicroRNA-30a inhibits epithelial-to-mesenchymal transition by targeting Snai1 and is downregulated in non-small cell lung cancer. International Journal of Cancer, 130, 2044–2053. doi:10.1002/ijc.26218. Kumarswamy, R., Mudduluru, G., Ceppi, P., Muppala, S., Kozlowski, M., Niklinski, J., et al. (2012). MicroRNA-30a inhibits epithelial-to-mesenchymal transition by targeting Snai1 and is downregulated in non-small cell lung cancer. International Journal of Cancer, 130, 2044–2053. doi:10.​1002/​ijc.​26218.
80.
go back to reference Liu, X., Wang, C., Chen, Z., Jin, Y., Wang, Y., Kolokythas, A., et al. (2011). MicroRNA-138 suppresses epithelial–mesenchymal transition in squamous cell carcinoma cell lines. Biochemistry Journal, 440(1), 23–31. doi:10.1042/BJ20111006. Liu, X., Wang, C., Chen, Z., Jin, Y., Wang, Y., Kolokythas, A., et al. (2011). MicroRNA-138 suppresses epithelial–mesenchymal transition in squamous cell carcinoma cell lines. Biochemistry Journal, 440(1), 23–31. doi:10.​1042/​BJ20111006.
81.
go back to reference Stinson, S., Lackner, M. R., Adai, A. T., Yu, N., Kim, H. J., O’Brien, C., et al. (2011). TRPS1 targeting by miR-221/222 promotes the epithelial-to-mesenchymal transition in breast cancer. Science Signaling, 4(177), ra41. doi:10.1126/scisignal.2001538.PubMed Stinson, S., Lackner, M. R., Adai, A. T., Yu, N., Kim, H. J., O’Brien, C., et al. (2011). TRPS1 targeting by miR-221/222 promotes the epithelial-to-mesenchymal transition in breast cancer. Science Signaling, 4(177), ra41. doi:10.​1126/​scisignal.​2001538.PubMed
82.
go back to reference Aigner, A. (2011). MicroRNAs (miRNAs) in cancer invasion and metastasis: Therapeutic approaches based on metastasis-related miRNAs. J Mol Med (Berl), 89(5), 445–457. doi:10.1007/s00109-010-0716-0. Aigner, A. (2011). MicroRNAs (miRNAs) in cancer invasion and metastasis: Therapeutic approaches based on metastasis-related miRNAs. J Mol Med (Berl), 89(5), 445–457. doi:10.​1007/​s00109-010-0716-0.
85.
go back to reference Wright, J. A., Richer, J. K., & Goodall, G. J. (2010). microRNAs and EMT in mammary cells and breast cancer. Journal of Mammary Gland Biology and Neoplasia, 15(2), 213–223. doi:10.1007/s10911-010-9183-z.PubMed Wright, J. A., Richer, J. K., & Goodall, G. J. (2010). microRNAs and EMT in mammary cells and breast cancer. Journal of Mammary Gland Biology and Neoplasia, 15(2), 213–223. doi:10.​1007/​s10911-010-9183-z.PubMed
86.
go back to reference Lombaerts, M., van Wezel, T., Philippo, K., Dierssen, J. W., Zimmerman, R. M., Oosting, J., et al. (2006). E-cadherin transcriptional downregulation by promoter methylation but not mutation is related to epithelial-to-mesenchymal transition in breast cancer cell lines. British Journal of Cancer, 94(5), 661–671. doi:10.1038/sj.bjc.6602996.PubMed Lombaerts, M., van Wezel, T., Philippo, K., Dierssen, J. W., Zimmerman, R. M., Oosting, J., et al. (2006). E-cadherin transcriptional downregulation by promoter methylation but not mutation is related to epithelial-to-mesenchymal transition in breast cancer cell lines. British Journal of Cancer, 94(5), 661–671. doi:10.​1038/​sj.​bjc.​6602996.PubMed
87.
go back to reference Tryndyak, V. P., Beland, F. A., & Pogribny, I. P. (2010). E-cadherin transcriptional down-regulation by epigenetic and microRNA-200 family alterations is related to mesenchymal and drug-resistant phenotypes in human breast cancer cells. International Journal of Cancer, 126(11), 2575–2583. Tryndyak, V. P., Beland, F. A., & Pogribny, I. P. (2010). E-cadherin transcriptional down-regulation by epigenetic and microRNA-200 family alterations is related to mesenchymal and drug-resistant phenotypes in human breast cancer cells. International Journal of Cancer, 126(11), 2575–2583.
88.
go back to reference Vrba, L., Jensen, T. J., Garbe, J. C., Heimark, R. L., Cress, A. E., Dickinson, S., et al. (2010). Role for DNA methylation in the regulation of miR-200c and miR-141 expression in normal and cancer cells. PLoS One, 5(1), e8697.PubMed Vrba, L., Jensen, T. J., Garbe, J. C., Heimark, R. L., Cress, A. E., Dickinson, S., et al. (2010). Role for DNA methylation in the regulation of miR-200c and miR-141 expression in normal and cancer cells. PLoS One, 5(1), e8697.PubMed
89.
go back to reference Ke, X. S., Qu, Y., Cheng, Y., Li, W. C., Rotter, V., Oyan, A. M., et al. (2010). Global profiling of histone and DNA methylation reveals epigenetic-based regulation of gene expression during epithelial to mesenchymal transition in prostate cells. BMC Genomics, 11, 669. doi:10.1186/1471-2164-11-669.PubMed Ke, X. S., Qu, Y., Cheng, Y., Li, W. C., Rotter, V., Oyan, A. M., et al. (2010). Global profiling of histone and DNA methylation reveals epigenetic-based regulation of gene expression during epithelial to mesenchymal transition in prostate cells. BMC Genomics, 11, 669. doi:10.​1186/​1471-2164-11-669.PubMed
90.
go back to reference Bernstein, B. E., Mikkelsen, T. S., Xie, X., Kamal, M., Huebert, D. J., Cuff, J., et al. (2006). A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell, 125(2), 315–326. doi:10.1016/j.cell.2006.02.041.PubMed Bernstein, B. E., Mikkelsen, T. S., Xie, X., Kamal, M., Huebert, D. J., Cuff, J., et al. (2006). A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell, 125(2), 315–326. doi:10.​1016/​j.​cell.​2006.​02.​041.PubMed
91.
go back to reference Cedar, H., & Bergman, Y. (2009). Linking DNA methylation and histone modification: patterns and paradigms. Nature Reviews Genetics, 10(5), 295–304. doi:10.1038/nrg2540.PubMed Cedar, H., & Bergman, Y. (2009). Linking DNA methylation and histone modification: patterns and paradigms. Nature Reviews Genetics, 10(5), 295–304. doi:10.​1038/​nrg2540.PubMed
92.
go back to reference Kaimori, A., Potter, J. J., Choti, M., Ding, Z., Mezey, E., & Koteish, A. A. (2010). Histone deacetylase inhibition suppresses the transforming growth factor beta1-induced epithelial-to-mesenchymal transition in hepatocytes. Hepatology, 52(3), 1033–1045.PubMed Kaimori, A., Potter, J. J., Choti, M., Ding, Z., Mezey, E., & Koteish, A. A. (2010). Histone deacetylase inhibition suppresses the transforming growth factor beta1-induced epithelial-to-mesenchymal transition in hepatocytes. Hepatology, 52(3), 1033–1045.PubMed
93.
go back to reference Yoshikawa, M., Hishikawa, K., Marumo, T., & Fujita, T. (2007). Inhibition of histone deacetylase activity suppresses epithelial-to-mesenchymal transition induced by TGF-beta1 in human renal epithelial cells. Journal of the American Society of Nephrology, 18(1), 58–65.PubMed Yoshikawa, M., Hishikawa, K., Marumo, T., & Fujita, T. (2007). Inhibition of histone deacetylase activity suppresses epithelial-to-mesenchymal transition induced by TGF-beta1 in human renal epithelial cells. Journal of the American Society of Nephrology, 18(1), 58–65.PubMed
94.
go back to reference Jordan, N. V., Johnson, G. L., & Abell, A. N. (2011). Tracking the intermediate stages of epithelial–mesenchymal transition in epithelial stem cells and cancer. Cell Cycle, 10(17), 2865–2873.PubMed Jordan, N. V., Johnson, G. L., & Abell, A. N. (2011). Tracking the intermediate stages of epithelial–mesenchymal transition in epithelial stem cells and cancer. Cell Cycle, 10(17), 2865–2873.PubMed
95.
go back to reference Abell, A. N., Jordan, N. V., Huang, W., Prat, A., Midland, A. A., Johnson, N. L., et al. (2011). MAP3K4/CBP-regulated H2B acetylation controls epithelial–mesenchymal transition in trophoblast stem cells. Cell Stem Cell, 8(5), 525–537.PubMed Abell, A. N., Jordan, N. V., Huang, W., Prat, A., Midland, A. A., Johnson, N. L., et al. (2011). MAP3K4/CBP-regulated H2B acetylation controls epithelial–mesenchymal transition in trophoblast stem cells. Cell Stem Cell, 8(5), 525–537.PubMed
96.
go back to reference Wels, C., Joshi, S., Koefinger, P., Bergler, H., & Schaider, H. (2011). Transcriptional activation of ZEB1 by Slug leads to cooperative regulation of the epithelial–mesenchymal transition-like phenotype in melanoma. The Journal of Investigative Dermatology, 131(9), 1877–1885. doi:10.1038/jid.2011.142.PubMed Wels, C., Joshi, S., Koefinger, P., Bergler, H., & Schaider, H. (2011). Transcriptional activation of ZEB1 by Slug leads to cooperative regulation of the epithelial–mesenchymal transition-like phenotype in melanoma. The Journal of Investigative Dermatology, 131(9), 1877–1885. doi:10.​1038/​jid.​2011.​142.PubMed
97.
go back to reference Casas, E., Kim, J., Bendesky, A., Ohno-Machado, L., Wolfe, C. J., & Yang, J. (2011). Snail2 is an essential mediator of Twist1-induced epithelial mesenchymal transition and metastasis. Cancer Research, 71(1), 245–254. doi:10.1158/0008-5472.CAN-10-2330.PubMed Casas, E., Kim, J., Bendesky, A., Ohno-Machado, L., Wolfe, C. J., & Yang, J. (2011). Snail2 is an essential mediator of Twist1-induced epithelial mesenchymal transition and metastasis. Cancer Research, 71(1), 245–254. doi:10.​1158/​0008-5472.​CAN-10-2330.PubMed
98.
go back to reference Taube, J. H., Herschkowitz, J. I., Komurov, K., Zhou, A. Y., Gupta, S., Yang, J., et al. (2010). Core epithelial-to-mesenchymal transition interactome gene-expression signature is associated with claudin-low and metaplastic breast cancer subtypes. Proceedings of the National Academy of Sciences of the United States of America, 107(35), 15449–15454. doi:10.1073/pnas.1004900107.PubMed Taube, J. H., Herschkowitz, J. I., Komurov, K., Zhou, A. Y., Gupta, S., Yang, J., et al. (2010). Core epithelial-to-mesenchymal transition interactome gene-expression signature is associated with claudin-low and metaplastic breast cancer subtypes. Proceedings of the National Academy of Sciences of the United States of America, 107(35), 15449–15454. doi:10.​1073/​pnas.​1004900107.PubMed
99.
go back to reference Chaffer, C. L., Brennan, J. P., Slavin, J. L., Blick, T., Thompson, E. W., & Williams, E. D. (2006). Mesenchymal-to-epithelial transition facilitates bladder cancer metastasis: role of fibroblast growth factor receptor-2. Cancer Research, 66(23), 11271–11278. doi:10.1158/0008-5472.CAN-06-2044.PubMed Chaffer, C. L., Brennan, J. P., Slavin, J. L., Blick, T., Thompson, E. W., & Williams, E. D. (2006). Mesenchymal-to-epithelial transition facilitates bladder cancer metastasis: role of fibroblast growth factor receptor-2. Cancer Research, 66(23), 11271–11278. doi:10.​1158/​0008-5472.​CAN-06-2044.PubMed
100.
go back to reference Korpal, M., Ell, B. J., Buffa, F. M., Ibrahim, T., Blanco, M. A., Celia-Terrassa, T., et al. (2011). Direct targeting of Sec23a by miR-200 s influences cancer cell secretome and promotes metastatic colonization. Nature Medicine, 17(9), 1101–1108. doi:10.1038/nm.2401.PubMed Korpal, M., Ell, B. J., Buffa, F. M., Ibrahim, T., Blanco, M. A., Celia-Terrassa, T., et al. (2011). Direct targeting of Sec23a by miR-200 s influences cancer cell secretome and promotes metastatic colonization. Nature Medicine, 17(9), 1101–1108. doi:10.​1038/​nm.​2401.PubMed
101.
go back to reference Chao, Y. L., Shepard, C. R., & Wells, A. (2010). Breast carcinoma cells re-express E-cadherin during mesenchymal to epithelial reverting transition. Molecular Cancer, 9, 179.PubMed Chao, Y. L., Shepard, C. R., & Wells, A. (2010). Breast carcinoma cells re-express E-cadherin during mesenchymal to epithelial reverting transition. Molecular Cancer, 9, 179.PubMed
102.
go back to reference Jeschke, U., Mylonas, I., Kuhn, C., Shabani, N., Kunert-Keil, C., Schindlbeck, C., et al. (2007). Expression of E-cadherin in human ductal breast cancer carcinoma in situ, invasive carcinomas, their lymph node metastases, their distant metastases, carcinomas with recurrence and in recurrence. Anticancer Research, 27(4A), 1969–1974.PubMed Jeschke, U., Mylonas, I., Kuhn, C., Shabani, N., Kunert-Keil, C., Schindlbeck, C., et al. (2007). Expression of E-cadherin in human ductal breast cancer carcinoma in situ, invasive carcinomas, their lymph node metastases, their distant metastases, carcinomas with recurrence and in recurrence. Anticancer Research, 27(4A), 1969–1974.PubMed
103.
go back to reference Park, D., Karesen, R., Axcrona, U., Noren, T., & Sauer, T. (2007). Expression pattern of adhesion molecules (E-cadherin, alpha-, beta-, gamma-catenin and claudin-7), their influence on survival in primary breast carcinoma, and their corresponding axillary lymph node metastasis. APMIS, 115(1), 52–65.PubMed Park, D., Karesen, R., Axcrona, U., Noren, T., & Sauer, T. (2007). Expression pattern of adhesion molecules (E-cadherin, alpha-, beta-, gamma-catenin and claudin-7), their influence on survival in primary breast carcinoma, and their corresponding axillary lymph node metastasis. APMIS, 115(1), 52–65.PubMed
104.
105.
go back to reference Garber, K. (2008). Epithelial-to-mesenchymal transition is important to metastasis, but questions remain. Journal of the National Cancer Institute, 100(4), 232–233. doi:10.1093/jnci/djn032.PubMed Garber, K. (2008). Epithelial-to-mesenchymal transition is important to metastasis, but questions remain. Journal of the National Cancer Institute, 100(4), 232–233. doi:10.​1093/​jnci/​djn032.PubMed
107.
108.
go back to reference Aslakson, C. J., & Miller, F. R. (1992). Selective events in the metastatic process defined by analysis of the sequential dissemination of subpopulations of a mouse mammary tumor. Cancer Research, 52(6), 1399–1405.PubMed Aslakson, C. J., & Miller, F. R. (1992). Selective events in the metastatic process defined by analysis of the sequential dissemination of subpopulations of a mouse mammary tumor. Cancer Research, 52(6), 1399–1405.PubMed
109.
go back to reference Zhang, H., Meng, F., Wu, S., Kreike, B., Sethi, S., Chen, W., et al. (2011). Engagement of I-branching beta}-1, 6-N-acetylglucosaminyltransferase 2 in breast cancer metastasis and TGF-{beta signaling. Cancer Research, 71(14), 4846–4856. doi:10.1158/0008-5472.CAN-11-0414.PubMed Zhang, H., Meng, F., Wu, S., Kreike, B., Sethi, S., Chen, W., et al. (2011). Engagement of I-branching beta}-1, 6-N-acetylglucosaminyltransferase 2 in breast cancer metastasis and TGF-{beta signaling. Cancer Research, 71(14), 4846–4856. doi:10.​1158/​0008-5472.​CAN-11-0414.PubMed
110.
go back to reference Lou, Y., Preobrazhenska, O., auf dem Keller, U., Sutcliffe, M., Barclay, L., McDonald, P. C., et al. (2008). Epithelial–mesenchymal transition (EMT) is not sufficient for spontaneous murine breast cancer metastasis. Developmental Dynamics, 237(10), 2755–2768. doi:10.1002/dvdy.21658.PubMed Lou, Y., Preobrazhenska, O., auf dem Keller, U., Sutcliffe, M., Barclay, L., McDonald, P. C., et al. (2008). Epithelial–mesenchymal transition (EMT) is not sufficient for spontaneous murine breast cancer metastasis. Developmental Dynamics, 237(10), 2755–2768. doi:10.​1002/​dvdy.​21658.PubMed
111.
go back to reference Futterman, M. A., Garcia, A. J., & Zamir, E. A. (2011). Evidence for partial epithelial-to-mesenchymal transition (pEMT) and recruitment of motile blastoderm edge cells during avian epiboly. Developmental Dynamics, 240(6), 1502–1511. doi:10.1002/dvdy.22607.PubMed Futterman, M. A., Garcia, A. J., & Zamir, E. A. (2011). Evidence for partial epithelial-to-mesenchymal transition (pEMT) and recruitment of motile blastoderm edge cells during avian epiboly. Developmental Dynamics, 240(6), 1502–1511. doi:10.​1002/​dvdy.​22607.PubMed
112.
go back to reference Chao, Y., Wu, Q., Acquafondata, M., Dhir, R., & Wells, A. (2011). Partial mesenchymal to epithelial reverting transition in breast and prostate cancer metastases. Cancer Microenviron, 5, 19–28. doi:10.1007/s12307-011-0085-4.PubMed Chao, Y., Wu, Q., Acquafondata, M., Dhir, R., & Wells, A. (2011). Partial mesenchymal to epithelial reverting transition in breast and prostate cancer metastases. Cancer Microenviron, 5, 19–28. doi:10.​1007/​s12307-011-0085-4.PubMed
113.
go back to reference Bruewer, M., Hopkins, A. M., Hobert, M. E., Nusrat, A., & Madara, J. L. (2004). RhoA, Rac1, and Cdc42 exert distinct effects on epithelial barrier via selective structural and biochemical modulation of junctional proteins and F-actin. American Journal of Physiology. Cell Physiology, 287(2), C327–C335. doi:10.1152/ajpcell.00087.200400087.2004.PubMed Bruewer, M., Hopkins, A. M., Hobert, M. E., Nusrat, A., & Madara, J. L. (2004). RhoA, Rac1, and Cdc42 exert distinct effects on epithelial barrier via selective structural and biochemical modulation of junctional proteins and F-actin. American Journal of Physiology. Cell Physiology, 287(2), C327–C335. doi:10.​1152/​ajpcell.​00087.​200400087.​2004.PubMed
114.
go back to reference Hay, E. D., & Zuk, A. (1995). Transformations between epithelium and mesenchyme: normal, pathological, and experimentally induced. American Journal of Kidney Diseases, 26(4), 678–690. doi:0272-6386(95)90610-X.PubMed Hay, E. D., & Zuk, A. (1995). Transformations between epithelium and mesenchyme: normal, pathological, and experimentally induced. American Journal of Kidney Diseases, 26(4), 678–690. doi:0272-6386(95)90610-X.PubMed
115.
go back to reference Pinkas, J., & Leder, P. (2002). MEK1 signaling mediates transformation and metastasis of EpH4 mammary epithelial cells independent of an epithelial to mesenchymal transition. Cancer Research, 62(16), 4781–4790.PubMed Pinkas, J., & Leder, P. (2002). MEK1 signaling mediates transformation and metastasis of EpH4 mammary epithelial cells independent of an epithelial to mesenchymal transition. Cancer Research, 62(16), 4781–4790.PubMed
116.
go back to reference Xue, C., Plieth, D., Venkov, C., Xu, C., & Neilson, E. G. (2003). The gatekeeper effect of epithelial–mesenchymal transition regulates the frequency of breast cancer metastasis. Cancer Research, 63(12), 3386–3394.PubMed Xue, C., Plieth, D., Venkov, C., Xu, C., & Neilson, E. G. (2003). The gatekeeper effect of epithelial–mesenchymal transition regulates the frequency of breast cancer metastasis. Cancer Research, 63(12), 3386–3394.PubMed
117.
go back to reference Mani, S. A., Guo, W., Liao, M. J., Eaton, E. N., Ayyanan, A., Zhou, A. Y., et al. (2008). The epithelial–mesenchymal transition generates cells with properties of stem cells. Cell, 133(4), 704–715. doi:10.1016/j.cell.2008.03.027.PubMed Mani, S. A., Guo, W., Liao, M. J., Eaton, E. N., Ayyanan, A., Zhou, A. Y., et al. (2008). The epithelial–mesenchymal transition generates cells with properties of stem cells. Cell, 133(4), 704–715. doi:10.​1016/​j.​cell.​2008.​03.​027.PubMed
118.
119.
go back to reference Aktas, B., Tewes, M., Fehm, T., Hauch, S., Kimmig, R., & Kasimir-Bauer, S. (2009). Stem cell and epithelial–mesenchymal transition markers are frequently overexpressed in circulating tumor cells of metastatic breast cancer patients. Breast Cancer Research, 11(4), R46. doi:10.1186/bcr2333.PubMed Aktas, B., Tewes, M., Fehm, T., Hauch, S., Kimmig, R., & Kasimir-Bauer, S. (2009). Stem cell and epithelial–mesenchymal transition markers are frequently overexpressed in circulating tumor cells of metastatic breast cancer patients. Breast Cancer Research, 11(4), R46. doi:10.​1186/​bcr2333.PubMed
120.
go back to reference Raimondi, C., Gradilone, A., Naso, G., Vincenzi, B., Petracca, A., Nicolazzo, C., et al. (2011). Epithelial–mesenchymal transition and stemness features in circulating tumor cells from breast cancer patients. Breast Cancer Research and Treatment, 130(2), 449–455. doi:10.1007/s10549-011-1373-x.PubMed Raimondi, C., Gradilone, A., Naso, G., Vincenzi, B., Petracca, A., Nicolazzo, C., et al. (2011). Epithelial–mesenchymal transition and stemness features in circulating tumor cells from breast cancer patients. Breast Cancer Research and Treatment, 130(2), 449–455. doi:10.​1007/​s10549-011-1373-x.PubMed
121.
go back to reference Kallergi, G., Papadaki, M. A., Politaki, E., Mavroudis, D., Georgoulias, V., & Agelaki, S. (2011). Epithelial to mesenchymal transition markers expressed in circulating tumour cells of early and metastatic breast cancer patients. Breast Cancer Research, 13(3), R59. doi:10.1186/bcr2896.PubMed Kallergi, G., Papadaki, M. A., Politaki, E., Mavroudis, D., Georgoulias, V., & Agelaki, S. (2011). Epithelial to mesenchymal transition markers expressed in circulating tumour cells of early and metastatic breast cancer patients. Breast Cancer Research, 13(3), R59. doi:10.​1186/​bcr2896.PubMed
122.
go back to reference Armstrong, A. J., Marengo, M. S., Oltean, S., Kemeny, G., Bitting, R. L., Turnbull, J. D., et al. (2011). Circulating tumor cells from patients with advanced prostate and breast cancer display both epithelial and mesenchymal markers. Molecular Cancer Research, 9(8), 997–1007. doi:10.1158/1541-7786.MCR-10-0490.PubMed Armstrong, A. J., Marengo, M. S., Oltean, S., Kemeny, G., Bitting, R. L., Turnbull, J. D., et al. (2011). Circulating tumor cells from patients with advanced prostate and breast cancer display both epithelial and mesenchymal markers. Molecular Cancer Research, 9(8), 997–1007. doi:10.​1158/​1541-7786.​MCR-10-0490.PubMed
123.
go back to reference Li, R., Liang, J., Ni, S., Zhou, T., Qing, X., Li, H., et al. (2010). A mesenchymal-to-epithelial transition initiates and is required for the nuclear reprogramming of mouse fibroblasts. Cell Stem Cell, 7(1), 51–63. doi:10.1016/j.stem.2010.04.014.PubMed Li, R., Liang, J., Ni, S., Zhou, T., Qing, X., Li, H., et al. (2010). A mesenchymal-to-epithelial transition initiates and is required for the nuclear reprogramming of mouse fibroblasts. Cell Stem Cell, 7(1), 51–63. doi:10.​1016/​j.​stem.​2010.​04.​014.PubMed
124.
go back to reference Samavarchi-Tehrani, P., Golipour, A., David, L., Sung, H. K., Beyer, T. A., Datti, A., et al. (2010). Functional genomics reveals a BMP-driven mesenchymal-to-epithelial transition in the initiation of somatic cell reprogramming. Cell Stem Cell, 7(1), 64–77. doi:10.1016/j.stem.2010.04.015.PubMed Samavarchi-Tehrani, P., Golipour, A., David, L., Sung, H. K., Beyer, T. A., Datti, A., et al. (2010). Functional genomics reveals a BMP-driven mesenchymal-to-epithelial transition in the initiation of somatic cell reprogramming. Cell Stem Cell, 7(1), 64–77. doi:10.​1016/​j.​stem.​2010.​04.​015.PubMed
125.
go back to reference Blick, T., Widodo, E., Hugo, H., Waltham, M., Lenburg, M. E., Neve, R. M., et al. (2008). Epithelial mesenchymal transition traits in human breast cancer cell lines. Clinical & Experimental Metastasis, 25(6), 629–642. doi:10.1007/s10585-008-9170-6. Blick, T., Widodo, E., Hugo, H., Waltham, M., Lenburg, M. E., Neve, R. M., et al. (2008). Epithelial mesenchymal transition traits in human breast cancer cell lines. Clinical & Experimental Metastasis, 25(6), 629–642. doi:10.​1007/​s10585-008-9170-6.
126.
go back to reference Neve, R. M., Chin, K., Fridlyand, J., Yeh, J., Baehner, F. L., Fevr, T., et al. (2006). A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell, 10(6), 515–527. doi:10.1016/j.ccr.2006.10.008.PubMed Neve, R. M., Chin, K., Fridlyand, J., Yeh, J., Baehner, F. L., Fevr, T., et al. (2006). A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell, 10(6), 515–527. doi:10.​1016/​j.​ccr.​2006.​10.​008.PubMed
127.
go back to reference Sayan, A. E., Griffiths, T. R., Pal, R., Browne, G. J., Ruddick, A., Yagci, T., et al. (2009). SIP1 protein protects cells from DNA damage-induced apoptosis and has independent prognostic value in bladder cancer. Proceedings of the National Academy of Sciences of the United States of America, 106(35), 14884–14889. doi:10.1073/pnas.0902042106.PubMed Sayan, A. E., Griffiths, T. R., Pal, R., Browne, G. J., Ruddick, A., Yagci, T., et al. (2009). SIP1 protein protects cells from DNA damage-induced apoptosis and has independent prognostic value in bladder cancer. Proceedings of the National Academy of Sciences of the United States of America, 106(35), 14884–14889. doi:10.​1073/​pnas.​0902042106.PubMed
128.
go back to reference Fuchs, B. C., Fujii, T., Dorfman, J. D., Goodwin, J. M., Zhu, A. X., Lanuti, M., et al. (2008). Epithelial-to-mesenchymal transition and integrin-linked kinase mediate sensitivity to epidermal growth factor receptor inhibition in human hepatoma cells. Cancer Research, 68(7), 2391–2399. doi:10.1158/0008-5472.CAN-07-2460.PubMed Fuchs, B. C., Fujii, T., Dorfman, J. D., Goodwin, J. M., Zhu, A. X., Lanuti, M., et al. (2008). Epithelial-to-mesenchymal transition and integrin-linked kinase mediate sensitivity to epidermal growth factor receptor inhibition in human hepatoma cells. Cancer Research, 68(7), 2391–2399. doi:10.​1158/​0008-5472.​CAN-07-2460.PubMed
129.
go back to reference Li, L. N., Zhang, H. D., Yuan, S. J., Yang, D. X., Wang, L., & Sun, Z. X. (2008). Differential sensitivity of colorectal cancer cell lines to artesunate is associated with expression of beta-catenin and E-cadherin. European Journal of Pharmacology, 588(1), 1–8. doi:10.1016/j.ejphar.2008.03.041.PubMed Li, L. N., Zhang, H. D., Yuan, S. J., Yang, D. X., Wang, L., & Sun, Z. X. (2008). Differential sensitivity of colorectal cancer cell lines to artesunate is associated with expression of beta-catenin and E-cadherin. European Journal of Pharmacology, 588(1), 1–8. doi:10.​1016/​j.​ejphar.​2008.​03.​041.PubMed
130.
go back to reference Sokol, J. P., Neil, J. R., Schiemann, B. J., & Schiemann, W. P. (2005). The use of cystatin C to inhibit epithelial–mesenchymal transition and morphological transformation stimulated by transforming growth factor-beta. Breast Cancer Research, 7(5), R844–R853. doi:10.1186/bcr1312.PubMed Sokol, J. P., Neil, J. R., Schiemann, B. J., & Schiemann, W. P. (2005). The use of cystatin C to inhibit epithelial–mesenchymal transition and morphological transformation stimulated by transforming growth factor-beta. Breast Cancer Research, 7(5), R844–R853. doi:10.​1186/​bcr1312.PubMed
131.
go back to reference Feldmann, G., Dhara, S., Fendrich, V., Bedja, D., Beaty, R., Mullendore, M., et al. (2007). Blockade of hedgehog signaling inhibits pancreatic cancer invasion and metastases: A new paradigm for combination therapy in solid cancers. Cancer Research, 67(5), 2187–2196. doi:10.1158/0008-5472.CAN-06-3281.PubMed Feldmann, G., Dhara, S., Fendrich, V., Bedja, D., Beaty, R., Mullendore, M., et al. (2007). Blockade of hedgehog signaling inhibits pancreatic cancer invasion and metastases: A new paradigm for combination therapy in solid cancers. Cancer Research, 67(5), 2187–2196. doi:10.​1158/​0008-5472.​CAN-06-3281.PubMed
132.
go back to reference Feldmann, G., Fendrich, V., McGovern, K., Bedja, D., Bisht, S., Alvarez, H., et al. (2008). An orally bioavailable small-molecule inhibitor of Hedgehog signaling inhibits tumor initiation and metastasis in pancreatic cancer. Molecular Cancer Therapeutics, 7(9), 2725–2735. doi:10.1158/1535-7163.MCT-08-0573.PubMed Feldmann, G., Fendrich, V., McGovern, K., Bedja, D., Bisht, S., Alvarez, H., et al. (2008). An orally bioavailable small-molecule inhibitor of Hedgehog signaling inhibits tumor initiation and metastasis in pancreatic cancer. Molecular Cancer Therapeutics, 7(9), 2725–2735. doi:10.​1158/​1535-7163.​MCT-08-0573.PubMed
133.
go back to reference Yauch, R. L., Januario, T., Eberhard, D. A., Cavet, G., Zhu, W., Fu, L., et al. (2005). Epithelial versus mesenchymal phenotype determines in vitro sensitivity and predicts clinical activity of erlotinib in lung cancer patients. Clinical Cancer Research, 11(24 Pt 1), 8686–8698. doi:10.1158/1078-0432.CCR-05-1492.PubMed Yauch, R. L., Januario, T., Eberhard, D. A., Cavet, G., Zhu, W., Fu, L., et al. (2005). Epithelial versus mesenchymal phenotype determines in vitro sensitivity and predicts clinical activity of erlotinib in lung cancer patients. Clinical Cancer Research, 11(24 Pt 1), 8686–8698. doi:10.​1158/​1078-0432.​CCR-05-1492.PubMed
134.
go back to reference Kajiyama, H., Shibata, K., Terauchi, M., Yamashita, M., Ino, K., Nawa, A., et al. (2007). Chemoresistance to paclitaxel induces epithelial–mesenchymal transition and enhances metastatic potential for epithelial ovarian carcinoma cells. International Journal of Oncology, 31(2), 277–283.PubMed Kajiyama, H., Shibata, K., Terauchi, M., Yamashita, M., Ino, K., Nawa, A., et al. (2007). Chemoresistance to paclitaxel induces epithelial–mesenchymal transition and enhances metastatic potential for epithelial ovarian carcinoma cells. International Journal of Oncology, 31(2), 277–283.PubMed
135.
go back to reference Konecny, G. E., Venkatesan, N., Yang, G., Dering, J., Ginther, C., Finn, R., et al. (2008). Activity of lapatinib a novel HER2 and EGFR dual kinase inhibitor in human endometrial cancer cells. British Journal of Cancer, 98(6), 1076–1084. doi:10.1038/sj.bjc.6604278.PubMed Konecny, G. E., Venkatesan, N., Yang, G., Dering, J., Ginther, C., Finn, R., et al. (2008). Activity of lapatinib a novel HER2 and EGFR dual kinase inhibitor in human endometrial cancer cells. British Journal of Cancer, 98(6), 1076–1084. doi:10.​1038/​sj.​bjc.​6604278.PubMed
136.
go back to reference Yang, Y., Pan, X., Lei, W., Wang, J., & Song, J. (2006). Transforming growth factor-beta1 induces epithelial-to-mesenchymal transition and apoptosis via a cell cycle-dependent mechanism. Oncogene, 25(55), 7235–7244.PubMed Yang, Y., Pan, X., Lei, W., Wang, J., & Song, J. (2006). Transforming growth factor-beta1 induces epithelial-to-mesenchymal transition and apoptosis via a cell cycle-dependent mechanism. Oncogene, 25(55), 7235–7244.PubMed
137.
go back to reference Vega, S., Morales, A. V., Ocana, O. H., Valdes, F., Fabregat, I., & Nieto, M. A. (2004). Snail blocks the cell cycle and confers resistance to cell death. Genes & Development, 18(10), 1131–1143. Vega, S., Morales, A. V., Ocana, O. H., Valdes, F., Fabregat, I., & Nieto, M. A. (2004). Snail blocks the cell cycle and confers resistance to cell death. Genes & Development, 18(10), 1131–1143.
138.
go back to reference Mejlvang, J., Kriajevska, M., Vandewalle, C., Chernova, T., Sayan, A. E., Berx, G., et al. (2007). Direct repression of cyclin D1 by SIP1 attenuates cell cycle progression in cells undergoing an epithelial mesenchymal transition. Molecular Biology of the Cell, 18(11), 4615–4624.PubMed Mejlvang, J., Kriajevska, M., Vandewalle, C., Chernova, T., Sayan, A. E., Berx, G., et al. (2007). Direct repression of cyclin D1 by SIP1 attenuates cell cycle progression in cells undergoing an epithelial mesenchymal transition. Molecular Biology of the Cell, 18(11), 4615–4624.PubMed
Metadata
Title
The rejuvenated scenario of epithelial–mesenchymal transition (EMT) and cancer metastasis
Authors
Fanyan Meng
Guojun Wu
Publication date
01-12-2012
Publisher
Springer US
Published in
Cancer and Metastasis Reviews / Issue 3-4/2012
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI
https://doi.org/10.1007/s10555-012-9379-3

Other articles of this Issue 3-4/2012

Cancer and Metastasis Reviews 3-4/2012 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine