Skip to main content
Top
Published in: BMC Cancer 1/2014

Open Access 01-12-2014 | Research article

MiR-200a inhibits epithelial-mesenchymal transition of pancreatic cancer stem cell

Authors: Yuhua Lu, Jingjing Lu, Xiaohong Li, Hui Zhu, Xiangjun Fan, Shajun Zhu, Yao Wang, Qingsong Guo, Lei Wang, Yan Huang, Mingyan Zhu, Zhiwei Wang

Published in: BMC Cancer | Issue 1/2014

Login to get access

Abstract

Background

Pancreatic cancer is one of the most aggressive cancers, and the aggressiveness of pancreatic cancer is in part due to its intrinsic and extrinsic drug resistance characteristics, which are also associated with the acquisition of epithelial-to-mesenchymal transition (EMT). Increasing evidence suggests that EMT-type cells share many biological characteristics with cancer stem-like cells. And miR-200 has been identified as a powerful regulator of EMT.

Methods

Cancer Stem Cells (CSCs) of human pancreatic cancer cell line PANC-1 were processed for CD24, CD44 and ESA multi-colorstaining, and sorted out on a BD FACS Aria II machine. RT-qPCR was performed using the miScript PCR Kit to assay the expression of miR-200 family. In order to find the role of miR-200a in the process of EMT, miR-200a mimic was transfected to CSCs.

Results

Pancreatic cancer cells with EMT phenotype displayed stem-like cell features characterized by the expression of cell surface markers CD24, CD44 and epithelial-specific antigen (ESA), which was associated with decreased expression of miR-200a. Moreover, overexpression of miR-200a was resulted in down-regulation of N-cadherin, ZEB1 and vimentin, but up-regulation of E-cadherin. In addition, miR-200a overexpression inhibited cell migration and invasion in CSCs.

Conclusion

In our study, we found that miR-200a played an important role in linking the characteristics of cancer stem-like cells with EMT-like cell signatures in pancreatic cancer. Selective elimination of cancer stem-like cells by reversing the EMT phenotype to mesenchymal-to-epithelial transition (MET) phenotype using novel agents would be useful for prevention and/or treatment of pancreatic cancer.
Appendix
Available only for authorised users
Literature
1.
go back to reference Xie CG, Wei SM, Chen JM, Xu XF, Cai JT, Chen QY, Jia LT: Down-regulation of GEP100 causes increase in E-cadherin levels and inhibits pancreatic cancer cell invasion. PLoS One. 7 (5): e37854- Xie CG, Wei SM, Chen JM, Xu XF, Cai JT, Chen QY, Jia LT: Down-regulation of GEP100 causes increase in E-cadherin levels and inhibits pancreatic cancer cell invasion. PLoS One. 7 (5): e37854-
2.
go back to reference Kallifatidis G, Rausch V, Baumann B, Apel A, Beckermann BM, Groth A, Mattern J, Li Z, Kolb A, Moldenhauer G, et al: Sulforaphane targets pancreatic tumour-initiating cells by NF-kappaB-induced antiapoptotic signalling. Gut. 2009, 58 (7): 949-963. 10.1136/gut.2008.149039.CrossRefPubMed Kallifatidis G, Rausch V, Baumann B, Apel A, Beckermann BM, Groth A, Mattern J, Li Z, Kolb A, Moldenhauer G, et al: Sulforaphane targets pancreatic tumour-initiating cells by NF-kappaB-induced antiapoptotic signalling. Gut. 2009, 58 (7): 949-963. 10.1136/gut.2008.149039.CrossRefPubMed
3.
go back to reference Bao B, Ali S, Kong D, Sarkar SH, Wang Z, Banerjee S, Aboukameel A, Padhye S, Philip PA, Sarkar FH: Anti-tumor activity of a novel compound-CDF is mediated by regulating miR-21, miR-200, and PTEN in pancreatic cancer. PLoS One. 6 (3): e17850- Bao B, Ali S, Kong D, Sarkar SH, Wang Z, Banerjee S, Aboukameel A, Padhye S, Philip PA, Sarkar FH: Anti-tumor activity of a novel compound-CDF is mediated by regulating miR-21, miR-200, and PTEN in pancreatic cancer. PLoS One. 6 (3): e17850-
4.
go back to reference Hermann PC, Bhaskar S, Cioffi M, Heeschen C: Cancer stem cells in solid tumors. Semin Cancer Biol. 20 (2): 77-84. Hermann PC, Bhaskar S, Cioffi M, Heeschen C: Cancer stem cells in solid tumors. Semin Cancer Biol. 20 (2): 77-84.
5.
go back to reference Shackleton M: Normal stem cells and cancer stem cells: similar and different. Semin Cancer Biol. 20 (2): 85-92. Shackleton M: Normal stem cells and cancer stem cells: similar and different. Semin Cancer Biol. 20 (2): 85-92.
6.
go back to reference Wen J, Park JY, Park KH, Chung HW, Bang S, Park SW, Song SY: Oct4 and Nanog expression is associated with early stages of pancreatic carcinogenesis. Pancreas. 39 (5): 622-626. Wen J, Park JY, Park KH, Chung HW, Bang S, Park SW, Song SY: Oct4 and Nanog expression is associated with early stages of pancreatic carcinogenesis. Pancreas. 39 (5): 622-626.
7.
go back to reference Li Y, VandenBoom TG, Kong D, Wang Z, Ali S, Philip PA, Sarkar FH: Up-regulation of miR-200 and let-7 by natural agents leads to the reversal of epithelial-to-mesenchymal transition in gemcitabine-resistant pancreatic cancer cells. Cancer Res. 2009, 69 (16): 6704-6712. 10.1158/0008-5472.CAN-09-1298.CrossRefPubMedPubMedCentral Li Y, VandenBoom TG, Kong D, Wang Z, Ali S, Philip PA, Sarkar FH: Up-regulation of miR-200 and let-7 by natural agents leads to the reversal of epithelial-to-mesenchymal transition in gemcitabine-resistant pancreatic cancer cells. Cancer Res. 2009, 69 (16): 6704-6712. 10.1158/0008-5472.CAN-09-1298.CrossRefPubMedPubMedCentral
8.
go back to reference Kurahara H, Takao S, Maemura K, Mataki Y, Kuwahata T, Maeda K, Ding Q, Sakoda M, Iino S, Ishigami S, et al: Epithelial-mesenchymal transition and mesenchymal-epithelial transition via regulation of ZEB-1 and ZEB-2 expression in pancreatic cancer. J Surg Oncol. 105 (7): 655-661. Kurahara H, Takao S, Maemura K, Mataki Y, Kuwahata T, Maeda K, Ding Q, Sakoda M, Iino S, Ishigami S, et al: Epithelial-mesenchymal transition and mesenchymal-epithelial transition via regulation of ZEB-1 and ZEB-2 expression in pancreatic cancer. J Surg Oncol. 105 (7): 655-661.
9.
go back to reference Watanabe S, Ueda Y, Akaboshi S, Hino Y, Sekita Y, Nakao M: HMGA2 maintains oncogenic RAS-induced epithelial-mesenchymal transition in human pancreatic cancer cells. Am J Pathol. 2009, 174 (3): 854-868. 10.2353/ajpath.2009.080523.CrossRefPubMedPubMedCentral Watanabe S, Ueda Y, Akaboshi S, Hino Y, Sekita Y, Nakao M: HMGA2 maintains oncogenic RAS-induced epithelial-mesenchymal transition in human pancreatic cancer cells. Am J Pathol. 2009, 174 (3): 854-868. 10.2353/ajpath.2009.080523.CrossRefPubMedPubMedCentral
10.
go back to reference Peinado H, Portillo F, Cano A: Transcriptional regulation of cadherins during development and carcinogenesis. Int J Dev Biol. 2004, 48 (5–6): 365-375.CrossRefPubMed Peinado H, Portillo F, Cano A: Transcriptional regulation of cadherins during development and carcinogenesis. Int J Dev Biol. 2004, 48 (5–6): 365-375.CrossRefPubMed
11.
go back to reference Santisteban M, Reiman JM, Asiedu MK, Behrens MD, Nassar A, Kalli KR, Haluska P, Ingle JN, Hartmann LC, Manjili MH, et al: Immune-induced epithelial to mesenchymal transition in vivo generates breast cancer stem cells. Cancer Res. 2009, 69 (7): 2887-2895. 10.1158/0008-5472.CAN-08-3343.CrossRefPubMedPubMedCentral Santisteban M, Reiman JM, Asiedu MK, Behrens MD, Nassar A, Kalli KR, Haluska P, Ingle JN, Hartmann LC, Manjili MH, et al: Immune-induced epithelial to mesenchymal transition in vivo generates breast cancer stem cells. Cancer Res. 2009, 69 (7): 2887-2895. 10.1158/0008-5472.CAN-08-3343.CrossRefPubMedPubMedCentral
12.
go back to reference Kasper S: Identification, characterization, and biological relevance of prostate cancer stem cells from clinical specimens. Urol Oncol. 2009, 27 (3): 301-303. 10.1016/j.urolonc.2008.12.012.CrossRefPubMedPubMedCentral Kasper S: Identification, characterization, and biological relevance of prostate cancer stem cells from clinical specimens. Urol Oncol. 2009, 27 (3): 301-303. 10.1016/j.urolonc.2008.12.012.CrossRefPubMedPubMedCentral
13.
go back to reference Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, et al: The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008, 133 (4): 704-715. 10.1016/j.cell.2008.03.027.CrossRefPubMedPubMedCentral Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, et al: The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008, 133 (4): 704-715. 10.1016/j.cell.2008.03.027.CrossRefPubMedPubMedCentral
14.
go back to reference Korpal M, Lee ES, Hu G, Kang Y: The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. J Biol Chem. 2008, 283 (22): 14910-14914. 10.1074/jbc.C800074200.CrossRefPubMedPubMedCentral Korpal M, Lee ES, Hu G, Kang Y: The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. J Biol Chem. 2008, 283 (22): 14910-14914. 10.1074/jbc.C800074200.CrossRefPubMedPubMedCentral
15.
go back to reference Bullock MD, Sayan AE, Packham GK, Mirnezami AH: MicroRNAs: critical regulators of epithelial to mesenchymal (EMT) and mesenchymal to epithelial transition (MET) in cancer progression. Biol Cell. 104 (1): 3-12. Bullock MD, Sayan AE, Packham GK, Mirnezami AH: MicroRNAs: critical regulators of epithelial to mesenchymal (EMT) and mesenchymal to epithelial transition (MET) in cancer progression. Biol Cell. 104 (1): 3-12.
16.
go back to reference Mongroo PS, Rustgi AK: The role of the miR-200 family in epithelial-mesenchymal transition. Cancer Biol Ther. 10 (3): 219-222. Mongroo PS, Rustgi AK: The role of the miR-200 family in epithelial-mesenchymal transition. Cancer Biol Ther. 10 (3): 219-222.
17.
go back to reference Hu X, Macdonald DM, Huettner PC, Feng Z, el Naqa IM, Schwarz JK, Mutch DG, Grigsby PW, Powell SN, Wang X: A miR-200 microRNA cluster as prognostic marker in advanced ovarian cancer. Gynecol Oncol. 2009, 114 (3): 457-464. 10.1016/j.ygyno.2009.05.022.CrossRefPubMed Hu X, Macdonald DM, Huettner PC, Feng Z, el Naqa IM, Schwarz JK, Mutch DG, Grigsby PW, Powell SN, Wang X: A miR-200 microRNA cluster as prognostic marker in advanced ovarian cancer. Gynecol Oncol. 2009, 114 (3): 457-464. 10.1016/j.ygyno.2009.05.022.CrossRefPubMed
18.
go back to reference Paterson EL, Kolesnikoff N, Gregory PA, Bert AG, Khew-Goodall Y, Goodall GJ: The microRNA-200 family regulates epithelial to mesenchymal transition. Sci World J. 2008, 8: 901-904.CrossRef Paterson EL, Kolesnikoff N, Gregory PA, Bert AG, Khew-Goodall Y, Goodall GJ: The microRNA-200 family regulates epithelial to mesenchymal transition. Sci World J. 2008, 8: 901-904.CrossRef
19.
go back to reference Schliekelman MJ, Gibbons DL, Faca VM, Creighton CJ, Rizvi ZH, Zhang Q, Wong CH, Wang H, Ungewiss C, Ahn YH, et al: Targets of the tumor suppressor miR-200 in regulation of the epithelial-mesenchymal transition in cancer. Cancer Res. 71 (24): 7670-7682. Schliekelman MJ, Gibbons DL, Faca VM, Creighton CJ, Rizvi ZH, Zhang Q, Wong CH, Wang H, Ungewiss C, Ahn YH, et al: Targets of the tumor suppressor miR-200 in regulation of the epithelial-mesenchymal transition in cancer. Cancer Res. 71 (24): 7670-7682.
20.
go back to reference Soubani O, Ali AS, Logna F, Ali S, Philip PA, Sarkar FH: Re-expression of miR-200 by novel approaches regulates the expression of PTEN and MT1-MMP in pancreatic cancer. Carcinogenesis. 33 (8): 1563-1571. Soubani O, Ali AS, Logna F, Ali S, Philip PA, Sarkar FH: Re-expression of miR-200 by novel approaches regulates the expression of PTEN and MT1-MMP in pancreatic cancer. Carcinogenesis. 33 (8): 1563-1571.
21.
go back to reference Chiou SH, Wang ML, Chou YT, Chen CJ, Hong CF, Hsieh WJ, Chang HT, Chen YS, Lin TW, Hsu HS, et al: Coexpression of Oct4 and Nanog enhances malignancy in lung adenocarcinoma by inducing cancer stem cell-like properties and epithelial-mesenchymal transdifferentiation. Cancer Res. 70 (24): 10433-10444. Chiou SH, Wang ML, Chou YT, Chen CJ, Hong CF, Hsieh WJ, Chang HT, Chen YS, Lin TW, Hsu HS, et al: Coexpression of Oct4 and Nanog enhances malignancy in lung adenocarcinoma by inducing cancer stem cell-like properties and epithelial-mesenchymal transdifferentiation. Cancer Res. 70 (24): 10433-10444.
22.
go back to reference Kong D, Li Y, Wang Z, Banerjee S, Ahmad A, Kim HR, Sarkar FH: miR-200 regulates PDGF-D-mediated epithelial-mesenchymal transition, adhesion, and invasion of prostate cancer cells. Stem Cells. 2009, 27 (8): 1712-1721. 10.1002/stem.101.CrossRefPubMedPubMedCentral Kong D, Li Y, Wang Z, Banerjee S, Ahmad A, Kim HR, Sarkar FH: miR-200 regulates PDGF-D-mediated epithelial-mesenchymal transition, adhesion, and invasion of prostate cancer cells. Stem Cells. 2009, 27 (8): 1712-1721. 10.1002/stem.101.CrossRefPubMedPubMedCentral
23.
go back to reference Polytarchou C, Iliopoulos D, Struhl K: An integrated transcriptional regulatory circuit that reinforces the breast cancer stem cell state. Proc Natl Acad Sci U S A. 109 (36): 14470-14475. Polytarchou C, Iliopoulos D, Struhl K: An integrated transcriptional regulatory circuit that reinforces the breast cancer stem cell state. Proc Natl Acad Sci U S A. 109 (36): 14470-14475.
24.
go back to reference Wang G, Guo X, Hong W, Liu Q, Wei T, Lu C, Gao L, Ye D, Zhou Y, Chen J, et al: Critical regulation of miR-200/ZEB2 pathway in Oct4/Sox2-induced mesenchymal-to-epithelial transition and induced pluripotent stem cell generation. Proc Natl Acad Sci U S A. 110 (8): 2858-2863. Wang G, Guo X, Hong W, Liu Q, Wei T, Lu C, Gao L, Ye D, Zhou Y, Chen J, et al: Critical regulation of miR-200/ZEB2 pathway in Oct4/Sox2-induced mesenchymal-to-epithelial transition and induced pluripotent stem cell generation. Proc Natl Acad Sci U S A. 110 (8): 2858-2863.
25.
go back to reference Shankar S, Nall D, Tang SN, Meeker D, Passarini J, Sharma J, Srivastava RK: Resveratrol inhibits pancreatic cancer stem cell characteristics in human and KrasG12D transgenic mice by inhibiting pluripotency maintaining factors and epithelial-mesenchymal transition. PLoS One. 6 (1): e16530- Shankar S, Nall D, Tang SN, Meeker D, Passarini J, Sharma J, Srivastava RK: Resveratrol inhibits pancreatic cancer stem cell characteristics in human and KrasG12D transgenic mice by inhibiting pluripotency maintaining factors and epithelial-mesenchymal transition. PLoS One. 6 (1): e16530-
26.
go back to reference Ischenko I, Seeliger H, Kleespies A, Angele MK, Eichhorn ME, Jauch KW, Bruns CJ: Pancreatic cancer stem cells: new understanding of tumorigenesis, clinical implications. Langenbecks Arch Surg. 395 (1): 1-10. Ischenko I, Seeliger H, Kleespies A, Angele MK, Eichhorn ME, Jauch KW, Bruns CJ: Pancreatic cancer stem cells: new understanding of tumorigenesis, clinical implications. Langenbecks Arch Surg. 395 (1): 1-10.
27.
go back to reference Wei HJ, Yin T, Zhu Z, Shi PF, Tian Y, Wang CY: Expression of CD44, CD24 and ESA in pancreatic adenocarcinoma cell lines varies with local microenvironment. Hepatobiliary Pancreat Dis Int. 10 (4): 428-434. Wei HJ, Yin T, Zhu Z, Shi PF, Tian Y, Wang CY: Expression of CD44, CD24 and ESA in pancreatic adenocarcinoma cell lines varies with local microenvironment. Hepatobiliary Pancreat Dis Int. 10 (4): 428-434.
28.
go back to reference Gach PC, Attayek PJ, Herrera G, Yeh JJ, Allbritton NL: Isolation and in vitro culture of rare cancer stem cells from patient-derived xenografts of pancreatic ductal adenocarcinoma. Anal Chem. 2013, 85 (15): 7271-7278. 10.1021/ac401165s.CrossRefPubMedPubMedCentral Gach PC, Attayek PJ, Herrera G, Yeh JJ, Allbritton NL: Isolation and in vitro culture of rare cancer stem cells from patient-derived xenografts of pancreatic ductal adenocarcinoma. Anal Chem. 2013, 85 (15): 7271-7278. 10.1021/ac401165s.CrossRefPubMedPubMedCentral
29.
go back to reference Fredebohm J, Boettcher M, Eisen C, Gaida MM, Heller A, Keleg S, Tost J, Greulich-Bode KM, Hotz-Wagenblatt A, Lathrop M, et al: Establishment and characterization of a highly tumourigenic and cancer stem cell enriched pancreatic cancer cell line as a well defined model system. PLoS One. 7 (11): e48503- Fredebohm J, Boettcher M, Eisen C, Gaida MM, Heller A, Keleg S, Tost J, Greulich-Bode KM, Hotz-Wagenblatt A, Lathrop M, et al: Establishment and characterization of a highly tumourigenic and cancer stem cell enriched pancreatic cancer cell line as a well defined model system. PLoS One. 7 (11): e48503-
30.
go back to reference Huang P, Wang CY, Gou SM, Wu HS, Liu T, Xiong JX: Isolation and biological analysis of tumor stem cells from pancreatic adenocarcinoma. World J Gastroenterol. 2008, 14 (24): 3903-3907. 10.3748/wjg.14.3903.CrossRefPubMedPubMedCentral Huang P, Wang CY, Gou SM, Wu HS, Liu T, Xiong JX: Isolation and biological analysis of tumor stem cells from pancreatic adenocarcinoma. World J Gastroenterol. 2008, 14 (24): 3903-3907. 10.3748/wjg.14.3903.CrossRefPubMedPubMedCentral
31.
go back to reference Ben-Ze’ev A: The use of two-dimensional gel electrophoresis in studies on the role of cytoskeletal plaque proteins as tumor suppressors. Electrophoresis. 1996, 17 (11): 1752-1763. 10.1002/elps.1150171113.CrossRefPubMed Ben-Ze’ev A: The use of two-dimensional gel electrophoresis in studies on the role of cytoskeletal plaque proteins as tumor suppressors. Electrophoresis. 1996, 17 (11): 1752-1763. 10.1002/elps.1150171113.CrossRefPubMed
32.
go back to reference Gou S, Liu T, Wang C, Yin T, Li K, Yang M, Zhou J: Establishment of clonal colony-forming assay for propagation of pancreatic cancer cells with stem cell properties. Pancreas. 2007, 34 (4): 429-435. 10.1097/MPA.0b013e318033f9f4.CrossRefPubMed Gou S, Liu T, Wang C, Yin T, Li K, Yang M, Zhou J: Establishment of clonal colony-forming assay for propagation of pancreatic cancer cells with stem cell properties. Pancreas. 2007, 34 (4): 429-435. 10.1097/MPA.0b013e318033f9f4.CrossRefPubMed
33.
go back to reference Musch T, Oz Y, Lyko F, Breiling A: Nucleoside drugs induce cellular differentiation by caspase-dependent degradation of stem cell factors. PLoS One. 5 (5): e10726- Musch T, Oz Y, Lyko F, Breiling A: Nucleoside drugs induce cellular differentiation by caspase-dependent degradation of stem cell factors. PLoS One. 5 (5): e10726-
34.
go back to reference Chiou SH, Yu CC, Huang CY, Lin SC, Liu CJ, Tsai TH, Chou SH, Chien CS, Ku HH, Lo JF: Positive correlations of Oct-4 and Nanog in oral cancer stem-like cells and high-grade oral squamous cell carcinoma. Clin Cancer Res. 2008, 14 (13): 4085-4095. 10.1158/1078-0432.CCR-07-4404.CrossRefPubMed Chiou SH, Yu CC, Huang CY, Lin SC, Liu CJ, Tsai TH, Chou SH, Chien CS, Ku HH, Lo JF: Positive correlations of Oct-4 and Nanog in oral cancer stem-like cells and high-grade oral squamous cell carcinoma. Clin Cancer Res. 2008, 14 (13): 4085-4095. 10.1158/1078-0432.CCR-07-4404.CrossRefPubMed
35.
go back to reference Luo W, Li S, Peng B, Ye Y, Deng X, Yao K: Embryonic stem cells markers SOX2, OCT4 and Nanog expression and their correlations with epithelial-mesenchymal transition in nasopharyngeal carcinoma. PLoS One. 8 (2): e56324- Luo W, Li S, Peng B, Ye Y, Deng X, Yao K: Embryonic stem cells markers SOX2, OCT4 and Nanog expression and their correlations with epithelial-mesenchymal transition in nasopharyngeal carcinoma. PLoS One. 8 (2): e56324-
36.
go back to reference Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, Vadas MA, Khew-Goodall Y, Goodall GJ: The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol. 2008, 10 (5): 593-601. 10.1038/ncb1722.CrossRefPubMed Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, Vadas MA, Khew-Goodall Y, Goodall GJ: The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol. 2008, 10 (5): 593-601. 10.1038/ncb1722.CrossRefPubMed
37.
go back to reference Sarkar FH, Li Y, Wang Z, Kong D: Pancreatic cancer stem cells and EMT in drug resistance and metastasis. Minerva Chir. 2009, 64 (5): 489-500.PubMedPubMedCentral Sarkar FH, Li Y, Wang Z, Kong D: Pancreatic cancer stem cells and EMT in drug resistance and metastasis. Minerva Chir. 2009, 64 (5): 489-500.PubMedPubMedCentral
38.
go back to reference Gavert N, Ben-Ze’ev A: Epithelial-mesenchymal transition and the invasive potential of tumors. Trends Mol Med. 2008, 14 (5): 199-209. 10.1016/j.molmed.2008.03.004.CrossRefPubMed Gavert N, Ben-Ze’ev A: Epithelial-mesenchymal transition and the invasive potential of tumors. Trends Mol Med. 2008, 14 (5): 199-209. 10.1016/j.molmed.2008.03.004.CrossRefPubMed
39.
go back to reference Cufi S, Vazquez-Martin A, Oliveras-Ferraros C, Martin-Castillo B, Joven J, Menendez JA: Metformin against TGFbeta-induced epithelial-to-mesenchymal transition (EMT): from cancer stem cells to aging-associated fibrosis. Cell Cycle. 9 (22): 4461-4468. Cufi S, Vazquez-Martin A, Oliveras-Ferraros C, Martin-Castillo B, Joven J, Menendez JA: Metformin against TGFbeta-induced epithelial-to-mesenchymal transition (EMT): from cancer stem cells to aging-associated fibrosis. Cell Cycle. 9 (22): 4461-4468.
40.
go back to reference Wu Y, Zhou BP: New insights of epithelial-mesenchymal transition in cancer metastasis. Acta Biochim Biophys Sin (Shanghai). 2008, 40 (7): 643-650. 10.1111/j.1745-7270.2008.00443.x.CrossRef Wu Y, Zhou BP: New insights of epithelial-mesenchymal transition in cancer metastasis. Acta Biochim Biophys Sin (Shanghai). 2008, 40 (7): 643-650. 10.1111/j.1745-7270.2008.00443.x.CrossRef
41.
go back to reference Zavadil J, Bottinger EP: TGF-beta and epithelial-to-mesenchymal transitions. Oncogene. 2005, 24 (37): 5764-5774. 10.1038/sj.onc.1208927.CrossRefPubMed Zavadil J, Bottinger EP: TGF-beta and epithelial-to-mesenchymal transitions. Oncogene. 2005, 24 (37): 5764-5774. 10.1038/sj.onc.1208927.CrossRefPubMed
42.
go back to reference Leong KG, Niessen K, Kulic I, Raouf A, Eaves C, Pollet I, Karsan A: Jagged1-mediated Notch activation induces epithelial-to-mesenchymal transition through Slug-induced repression of E-cadherin. J Exp Med. 2007, 204 (12): 2935-2948. 10.1084/jem.20071082.CrossRefPubMedPubMedCentral Leong KG, Niessen K, Kulic I, Raouf A, Eaves C, Pollet I, Karsan A: Jagged1-mediated Notch activation induces epithelial-to-mesenchymal transition through Slug-induced repression of E-cadherin. J Exp Med. 2007, 204 (12): 2935-2948. 10.1084/jem.20071082.CrossRefPubMedPubMedCentral
43.
go back to reference Pirozzi G, Tirino V, Camerlingo R, Franco R, la Rocca A, Liguori E, Martucci N, Paino F, Normanno N, Rocco G: Epithelial to mesenchymal transition by TGFbeta-1 induction increases stemness characteristics in primary non small cell lung cancer cell line. PLoS One. 6 (6): e21548- Pirozzi G, Tirino V, Camerlingo R, Franco R, la Rocca A, Liguori E, Martucci N, Paino F, Normanno N, Rocco G: Epithelial to mesenchymal transition by TGFbeta-1 induction increases stemness characteristics in primary non small cell lung cancer cell line. PLoS One. 6 (6): e21548-
Metadata
Title
MiR-200a inhibits epithelial-mesenchymal transition of pancreatic cancer stem cell
Authors
Yuhua Lu
Jingjing Lu
Xiaohong Li
Hui Zhu
Xiangjun Fan
Shajun Zhu
Yao Wang
Qingsong Guo
Lei Wang
Yan Huang
Mingyan Zhu
Zhiwei Wang
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2014
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-14-85

Other articles of this Issue 1/2014

BMC Cancer 1/2014 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