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SIP1/ZEB2 induces EMT by repressing genes of different epithelial cell-cell junctions
Open accessAbstract
SIP1/ZEB2 is a member of the deltaEF-1 family of two-handed zinc finger nuclear factors. The expression of these transcription factors is associated with epithelial mesenchymal transitions (EMT) during development. SIP1 is also expressed in some breast cancer cell lines and was detected in intestinal gastric carcinomas, where its expression is inversely correlated with that of E-cadherin. Here, we show that expression of SIP1 in human epithelial cells results in a clear morphological change from an epithelial to a mesenchymal phenotype. Induction of this epithelial dedifferentiation was accompanied by repression of several cell junctional proteins, with concomitant repression of their mRNA levels. Besides E-cadherin, other genes coding for crucial proteins of tight junctions, desmosomes and gap junctions were found to be transcriptionally regulated by the transcriptional repressor SIP1. Moreover, study of the promoter regions of selected genes by luciferase reporter assays and chromatin immunoprecipitation shows that repression is directly mediated by SIP1. These data indicate that, during epithelial dedifferentiation, SIP1 represses in a coordinated manner the transcription of genes coding for junctional proteins contributing to the dedifferentiated state; this repression occurs by a general mechanism mediated by Smad Interacting Protein 1 (SIP1)-binding sites.
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Ohkubo, T., & Ozawa, M. (2004) · Journal of Cell Science · doi:10.1242/jcs.01004 · Cited by 322
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TGF-β-induced epithelial to mesenchymal transition
Xu, J., Lamouille, S., & Derynck, R. (2009) · Cell Research · doi:10.1038/cr.2009.5 · Cited by 2,804
Regulatory networks defining EMT during cancer initiation and progression
Craene, B. D., & Berx, G. (2013) · Nature Reviews Cancer · doi:10.1038/nrc3447 · Cited by 2,487
Signaling mechanisms of the epithelial-mesenchymal transition
Gonzalez, D. M., & Medici, D. (2014) · Science Signaling · doi:10.1126/scisignal.2005189 · Cited by 1,721
Yadav, A., Kumar, B., Datta, J., Teknos, T. N., & Kumar, P. (2011) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-11-0271 · Cited by 503
Metadata
- Authors
- Vandewalle, C.
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-11-27
- Volume
- 33
- Issue
- 20
- Pages
- 6566-6578
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- OpenAlex
- W2022916389
- Cited by
- 542
- References
- 1
- FWCI
- 7.07
- Type
- journal article
- Language
- en
- Open access
- gold
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- Vandewalle, C. (2005). SIP1/ZEB2 induces EMT by repressing genes of different epithelial cell-cell junctions. Nucleic Acids Research. https://doi.org/10.1093/nar/gki965
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