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Published in: Tumor Biology 2/2014

01-02-2014 | Research Article

Notch-1-mediated esophageal carcinoma EC-9706 cell invasion and metastasis by inducing epithelial–mesenchymal transition through Snail

Authors: Tao Wang, Xiaoyan Xuan, Linping Pian, Ping Gao, Hong Xu, Yuling Zheng, Wenqiao Zang, Guoqiang Zhao

Published in: Tumor Biology | Issue 2/2014

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Abstract

Notch has recently been shown to promote epithelial-to-mesenchymal transition (EMT) by involving in the EMT process that occurs during tumor progression and converts polarized epithelial cells into motile, invasive cells. However, it is still unclear whether the Notch signaling pathway is associated with the regulation of EMT in esophageal carcinoma. The present study explored Notch-1-mediated esophageal carcinoma EC-9706 cell invasion and metastasis by inducing epithelial–mesenchymal transition through Snail. The results demonstrated that the inhibition of Notch-1 expression in the esophageal carcinoma cell line EC-9706 could suppress the occurrence of EMT and at the same time could decrease the invasion and metastasis ability of the EC-9706 cells, indicative of its role in EMT. Snail is a transcriptional repressor of E-cadherin. We found that with the inhibition of Notch-1 expression in the esophageal carcinoma cell line EC-9706, the expression of Snail also decreased. Mechanistic studies showed that the up-expression of Snail in the EC-9706 cells restored the suppression of EMT regulated by Notch-1 inhibition, suggesting the role of Snail in Notch-1-mediated EMT. At the same time, the up-expression of Snail in the EC-9706 cells could also rescue the invasion and metastasis ability inhibited by Notch-1 siRNA. Taken together, our results had revealed that Notch-1 could participate in the invasion and metastasis of esophageal carcinoma through EMT via Snail. This study indicated that Notch-1 might be a useful target for esophageal carcinoma prevention and therapy.
Literature
1.
go back to reference Lu JC, Tao H, Zhang YQ, Zha WW, Qian PD, Li F, et al. Extent of prophylactic postoperative radiotherapy after radical surgery of thoracic esophageal squamous cell carcinoma. Dis Esophagus. 2008;21(6):502–7.PubMedCrossRef Lu JC, Tao H, Zhang YQ, Zha WW, Qian PD, Li F, et al. Extent of prophylactic postoperative radiotherapy after radical surgery of thoracic esophageal squamous cell carcinoma. Dis Esophagus. 2008;21(6):502–7.PubMedCrossRef
2.
go back to reference Pai A, Sonawane S, Purandare NC, Rangarajan V, Ramadwar M, Pramesh CS, et al. Penile metastasis from esophageal squamous carcinoma after curative resection. Ann Thorac Cardiovasc Surg. 2008;14(4):238–41.PubMed Pai A, Sonawane S, Purandare NC, Rangarajan V, Ramadwar M, Pramesh CS, et al. Penile metastasis from esophageal squamous carcinoma after curative resection. Ann Thorac Cardiovasc Surg. 2008;14(4):238–41.PubMed
3.
go back to reference Foroni C, Broggini M, Generali D, Damia G. Epithelial-mesenchymal transition and breast cancer: role, molecular mechanisms and clinical impact. Cancer Treat Rev. 2012;38(6):689–97.PubMedCrossRef Foroni C, Broggini M, Generali D, Damia G. Epithelial-mesenchymal transition and breast cancer: role, molecular mechanisms and clinical impact. Cancer Treat Rev. 2012;38(6):689–97.PubMedCrossRef
4.
go back to reference Xiong H, Hong J, Du W, Lin YW, Ren LL, Wang YC, et al. Roles of STAT3 and ZEB1 proteins in E-cadherin down-regulation and human colorectal cancer epithelial-mesenchymal transition. J Biol Chem. 2012;287(8):5819–32.PubMedCrossRef Xiong H, Hong J, Du W, Lin YW, Ren LL, Wang YC, et al. Roles of STAT3 and ZEB1 proteins in E-cadherin down-regulation and human colorectal cancer epithelial-mesenchymal transition. J Biol Chem. 2012;287(8):5819–32.PubMedCrossRef
5.
go back to reference Voulgari A, Pintzas A. Epithelial-mesenchymal transition in cancer metastasis: mechanisms, markers and strategies to overcome drug resistance in the clinic. Biochim Biophys Acta. 2009;1796(2):75–90.PubMed Voulgari A, Pintzas A. Epithelial-mesenchymal transition in cancer metastasis: mechanisms, markers and strategies to overcome drug resistance in the clinic. Biochim Biophys Acta. 2009;1796(2):75–90.PubMed
6.
go back to reference Peinado H, Olmeda D, Cano A. Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nat Rev Cancer. 2007;7(6):415–28.PubMedCrossRef Peinado H, Olmeda D, Cano A. Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nat Rev Cancer. 2007;7(6):415–28.PubMedCrossRef
7.
go back to reference Reichl P, Haider C, Grubinger M, Mikulits W. TGF-β in epithelial to mesenchymal transition and metastasis of liver carcinoma. Curr Pharm Des. 2012;18(27):4135–47.PubMedCrossRef Reichl P, Haider C, Grubinger M, Mikulits W. TGF-β in epithelial to mesenchymal transition and metastasis of liver carcinoma. Curr Pharm Des. 2012;18(27):4135–47.PubMedCrossRef
8.
go back to reference Shimokawa M, Haraguchi M, Kobayashi W, Higashi Y, Matsushita S, Kawai K, et al. The transcription factor Snail expressed in cutaneous squamous cell carcinoma induces epithelial-mesenchymal transition and down-regulates COX-2. Biochem Biophys Res Commun. 2013;430(3):1078–82.PubMedCrossRef Shimokawa M, Haraguchi M, Kobayashi W, Higashi Y, Matsushita S, Kawai K, et al. The transcription factor Snail expressed in cutaneous squamous cell carcinoma induces epithelial-mesenchymal transition and down-regulates COX-2. Biochem Biophys Res Commun. 2013;430(3):1078–82.PubMedCrossRef
9.
go back to reference Kume K, Haraguchi M, Hijioka H, Ishida T, Miyawaki A, Nakamura N, et al. The transcription factor Snail enhanced the degradation of E-cadherin and desmoglein 2 in oral squamous cell carcinoma cells. Biochem Biophys Res Commun. 2013;430(3):889–94.PubMedCrossRef Kume K, Haraguchi M, Hijioka H, Ishida T, Miyawaki A, Nakamura N, et al. The transcription factor Snail enhanced the degradation of E-cadherin and desmoglein 2 in oral squamous cell carcinoma cells. Biochem Biophys Res Commun. 2013;430(3):889–94.PubMedCrossRef
10.
go back to reference Colas E, Pedrola N, Devis L, Ertekin T, Campoy I, Martínez E, et al. The EMT signaling pathways in endometrial carcinoma. Clin Transl Oncol. 2012;14(10):715–20.PubMedCrossRef Colas E, Pedrola N, Devis L, Ertekin T, Campoy I, Martínez E, et al. The EMT signaling pathways in endometrial carcinoma. Clin Transl Oncol. 2012;14(10):715–20.PubMedCrossRef
11.
go back to reference Chen W, Zhang H, Wang J, Cao G, Dong Z, Su H, et al. Lentiviral-mediated gene silencing of Notch-4 inhibits in vitro proliferation and perineural invasion of ACC-M cells. Oncol Rep. 2013;29(5):1797–804.PubMed Chen W, Zhang H, Wang J, Cao G, Dong Z, Su H, et al. Lentiviral-mediated gene silencing of Notch-4 inhibits in vitro proliferation and perineural invasion of ACC-M cells. Oncol Rep. 2013;29(5):1797–804.PubMed
12.
go back to reference Yatim A, Benne C, Sobhian B, Laurent-Chabalier S, Deas O, Judde JG, et al. NOTCH1 nuclear interactome reveals key regulators of its transcriptional activity and oncogenic function. Mol Cell. 2012;48(3):445–58.PubMedCentralPubMedCrossRef Yatim A, Benne C, Sobhian B, Laurent-Chabalier S, Deas O, Judde JG, et al. NOTCH1 nuclear interactome reveals key regulators of its transcriptional activity and oncogenic function. Mol Cell. 2012;48(3):445–58.PubMedCentralPubMedCrossRef
13.
go back to reference Hu YY, Zheng MH, Zhang R, Liang YM, Han H. Notch signaling pathway and cancer metastasis. Adv Exp Med Biol. 2012;727:186–98.PubMedCrossRef Hu YY, Zheng MH, Zhang R, Liang YM, Han H. Notch signaling pathway and cancer metastasis. Adv Exp Med Biol. 2012;727:186–98.PubMedCrossRef
14.
go back to reference Matsuno Y, Coelho AL, Jarai G, Westwick J, Hogaboam CM. Notch signaling mediates TGF-β1-induced epithelial-mesenchymal transition through the induction of Snai1. Int J Biochem Cell Biol. 2012;44(5):776–89.PubMedCrossRef Matsuno Y, Coelho AL, Jarai G, Westwick J, Hogaboam CM. Notch signaling mediates TGF-β1-induced epithelial-mesenchymal transition through the induction of Snai1. Int J Biochem Cell Biol. 2012;44(5):776–89.PubMedCrossRef
15.
go back to reference Güngör C, Zander H, Effenberger KE, Vashist YK, Kalinina T, Izbicki JR, et al. Notch signaling activated by replication stress-induced expression of midkine drives epithelial-mesenchymal transition and chemoresistance in pancreatic cancer. Cancer Res. 2011;71(14):5009–19.PubMedCrossRef Güngör C, Zander H, Effenberger KE, Vashist YK, Kalinina T, Izbicki JR, et al. Notch signaling activated by replication stress-induced expression of midkine drives epithelial-mesenchymal transition and chemoresistance in pancreatic cancer. Cancer Res. 2011;71(14):5009–19.PubMedCrossRef
16.
go back to reference Kong D, Li Y, Wang Z, Banerjee S, Ahmad A, Kim HR, et al. The MiR-200 regulates PDGF-D mediated epithelial-mesenchymal transition, adhesion and invasion of prostate cancer cells. Stem Cells. 2009;27(8):1712–21.PubMedCentralPubMedCrossRef Kong D, Li Y, Wang Z, Banerjee S, Ahmad A, Kim HR, et al. The MiR-200 regulates PDGF-D mediated epithelial-mesenchymal transition, adhesion and invasion of prostate cancer cells. Stem Cells. 2009;27(8):1712–21.PubMedCentralPubMedCrossRef
17.
go back to reference Timmerman LA, Grego-Bessa J, Raya A, Bertrán E, Pérez-Pomares JM, Díez J, et al. Notch promotes epithelial-mesenchymal transition during cardiac development and oncogenic transformation. Genes Dev. 2004;18(1):99–115.PubMedCrossRef Timmerman LA, Grego-Bessa J, Raya A, Bertrán E, Pérez-Pomares JM, Díez J, et al. Notch promotes epithelial-mesenchymal transition during cardiac development and oncogenic transformation. Genes Dev. 2004;18(1):99–115.PubMedCrossRef
18.
go back to reference Alves CC, Carneiro F, Hoefler H, Becker KF. Role of the epithelial-mesenchymal transition regulator Slug in primary human cancers. Front Biosci. 2009;14:3035–50.CrossRef Alves CC, Carneiro F, Hoefler H, Becker KF. Role of the epithelial-mesenchymal transition regulator Slug in primary human cancers. Front Biosci. 2009;14:3035–50.CrossRef
19.
go back to reference Korpal M, Kang Y. The emerging role of miR-200 family of microRNAs in epithelial-mesenchymal transition and cancer metastasis. RNA Biol. 2008;5(3):115–9.PubMedCentralPubMedCrossRef Korpal M, Kang Y. The emerging role of miR-200 family of microRNAs in epithelial-mesenchymal transition and cancer metastasis. RNA Biol. 2008;5(3):115–9.PubMedCentralPubMedCrossRef
21.
go back to reference Wang Z, Ahmad A, Li Y, Azmi AS, Miele L, Sarkar FH. Targeting notch to eradicate pancreatic cancer stem cells for cancer therapy. Anticancer Res. 2011;31(4):1105–13.PubMed Wang Z, Ahmad A, Li Y, Azmi AS, Miele L, Sarkar FH. Targeting notch to eradicate pancreatic cancer stem cells for cancer therapy. Anticancer Res. 2011;31(4):1105–13.PubMed
22.
go back to reference Wang Z, Li Y, Kong D, Banerjee S, Ahmad A, Azmi AS, et al. Acquisition of epithelial-mesenchymal transition phenotype of gemcitabine-resistant pancreatic cancer cells is linked with activation of the notch signaling pathway. Cancer Res. 2009;69(6):2400–7.PubMedCentralPubMedCrossRef Wang Z, Li Y, Kong D, Banerjee S, Ahmad A, Azmi AS, et al. Acquisition of epithelial-mesenchymal transition phenotype of gemcitabine-resistant pancreatic cancer cells is linked with activation of the notch signaling pathway. Cancer Res. 2009;69(6):2400–7.PubMedCentralPubMedCrossRef
23.
go back to reference Reedijk M, Odorcic S, Chang L, Zhang H, Miller N, McCready DR, et al. High-level coexpression of JAG1 and NOTCH1 is observed in human breast cancer and is associated with poor overall survival. Cancer Res. 2005;65(18):8530–857.PubMedCrossRef Reedijk M, Odorcic S, Chang L, Zhang H, Miller N, McCready DR, et al. High-level coexpression of JAG1 and NOTCH1 is observed in human breast cancer and is associated with poor overall survival. Cancer Res. 2005;65(18):8530–857.PubMedCrossRef
24.
go back to reference Rizzo P, Miao H, D'Souza G, Osipo C, Song LL, Yun J, et al. Cross-talk between notch and the estrogen receptor in breast cancer suggests novel therapeutic approaches. Cancer Res. 2008;68(13):5226–35.PubMedCrossRef Rizzo P, Miao H, D'Souza G, Osipo C, Song LL, Yun J, et al. Cross-talk between notch and the estrogen receptor in breast cancer suggests novel therapeutic approaches. Cancer Res. 2008;68(13):5226–35.PubMedCrossRef
25.
go back to reference Sjölund J, Johansson M, Manna S, Norin C, Pietras A, Beckman S, et al. Suppression of renal cell carcinoma growth by inhibition of Notch signaling in vitro and in vivo. J Clin Invest. 2008;118(1):217–28.PubMedCentralPubMedCrossRef Sjölund J, Johansson M, Manna S, Norin C, Pietras A, Beckman S, et al. Suppression of renal cell carcinoma growth by inhibition of Notch signaling in vitro and in vivo. J Clin Invest. 2008;118(1):217–28.PubMedCentralPubMedCrossRef
26.
go back to reference Niessen K, Fu Y, Chang L, Hoodless PA, McFadden D, Karsan A. Slug is a direct Notch target required for initiation of cardiac cushion cellularization. J Cell Biol. 2008;182(2):315–25.PubMedCrossRef Niessen K, Fu Y, Chang L, Hoodless PA, McFadden D, Karsan A. Slug is a direct Notch target required for initiation of cardiac cushion cellularization. J Cell Biol. 2008;182(2):315–25.PubMedCrossRef
27.
go back to reference Sahlgren C, Gustafsson MV, Jin S, Poellinger L, Lendahl U. Notch signaling mediates hypoxia-induced tumor cell migration and invasion. Proc Natl Acad Sci U S A. 2008;105(17):6392–7.PubMedCentralPubMedCrossRef Sahlgren C, Gustafsson MV, Jin S, Poellinger L, Lendahl U. Notch signaling mediates hypoxia-induced tumor cell migration and invasion. Proc Natl Acad Sci U S A. 2008;105(17):6392–7.PubMedCentralPubMedCrossRef
28.
go back to reference Zavadil J, Cermak L, Soto-Nieves N, Böttinger EP. Integration of TGF-beta/Smad and Jagged1/Notch signalling in epithelial-to-mesenchymal transition. EMBO J. 2004;23(5):1155–65.PubMedCrossRef Zavadil J, Cermak L, Soto-Nieves N, Böttinger EP. Integration of TGF-beta/Smad and Jagged1/Notch signalling in epithelial-to-mesenchymal transition. EMBO J. 2004;23(5):1155–65.PubMedCrossRef
29.
go back to reference Ding SZ, Yang YX, Li XL, Michelli-Rivera A, Han SY, Wang L, et al. Epithelial-mesenchymal transition during oncogenic transformation induced by hexavalent chromium involves reactive oxygen species-dependent mechanism in lung epithelial cells. Toxicol Appl Pharmacol. 2013;269(1):61–71.PubMedCrossRef Ding SZ, Yang YX, Li XL, Michelli-Rivera A, Han SY, Wang L, et al. Epithelial-mesenchymal transition during oncogenic transformation induced by hexavalent chromium involves reactive oxygen species-dependent mechanism in lung epithelial cells. Toxicol Appl Pharmacol. 2013;269(1):61–71.PubMedCrossRef
30.
go back to reference Smith BN, Odero-Marah VA. The role of Snail in prostate cancer. Cell AdhesMigr. 2012;6(5):433–4341. Smith BN, Odero-Marah VA. The role of Snail in prostate cancer. Cell AdhesMigr. 2012;6(5):433–4341.
31.
go back to reference Tiwari N, Gheldof A, Tatari M, Christofori G. EMT as the ultimate survival mechanism of cancer cells. Semin Cancer Biol. 2012;22(3):194–207.PubMedCrossRef Tiwari N, Gheldof A, Tatari M, Christofori G. EMT as the ultimate survival mechanism of cancer cells. Semin Cancer Biol. 2012;22(3):194–207.PubMedCrossRef
32.
go back to reference Sato M, Shames DS, Hasegawa Y. Emerging evidence of epithelial-to-mesenchymal transition in lung carcinogenesis. Respirology. 2012;17(7):1048–59.PubMedCrossRef Sato M, Shames DS, Hasegawa Y. Emerging evidence of epithelial-to-mesenchymal transition in lung carcinogenesis. Respirology. 2012;17(7):1048–59.PubMedCrossRef
Metadata
Title
Notch-1-mediated esophageal carcinoma EC-9706 cell invasion and metastasis by inducing epithelial–mesenchymal transition through Snail
Authors
Tao Wang
Xiaoyan Xuan
Linping Pian
Ping Gao
Hong Xu
Yuling Zheng
Wenqiao Zang
Guoqiang Zhao
Publication date
01-02-2014
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 2/2014
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-013-1159-3

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