Reference : Regulation of p63 Isoforms by Snail and Slug Transcription Factors in Human Squamous Cel...
Scientific journals : Article
Human health sciences : Oncology
http://hdl.handle.net/2268/40469
Regulation of p63 Isoforms by Snail and Slug Transcription Factors in Human Squamous Cell Carcinoma.
English
Herfs, Michael mailto [Université de Liège - ULg > > > Doct. sc. bioméd. & pharma. (Bologne)]
Hubert, Pascale mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques >]
Suarez-Carmona, Meggy mailto [Université de Liège - ULg > > > 2e an. master sc. bioméd., fin. approf.]
Reschner, Anca mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques >]
Saussez, S. mailto [> > > >]
Berx, G. mailto [> > > >]
Savagner, P. mailto [> > > >]
Boniver, Jacques mailto [Centre Hospitalier Universitaire de Liège - CHU > > Anatomie pathologique >]
Delvenne, Philippe mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques >]
2010
American Journal of Pathology
American Society for Investigative Pathology
176
4
1941-1949
Yes (verified by ORBi)
International
0002-9440
1525-2191
Bethesda
MD
[en] P63 ; tumorigenesis
[en] TP63 is a p53-related gene that contains two alternative promoters, which give rise to transcripts that encode proteins with (TAp63) or without (DeltaNp63) an amino-transactivating domain. Whereas the expression of p63 is required for proper development of epithelial structures, the role of p63 in tumorigenesis remains unclear. Here, we investigated the role of Snail and Slug transcription factors, known to promote epithelial-to-mesenchymal transitions during development and cancer, in the regulation of p63 isoforms in human squamous cell carcinoma (SCC). In the present study, we observed that the expressions of DeltaN and TAp63 isoforms were, respectively, down- and up-regulated by both Snail and Slug. However, the induction of TAp63 was not directly caused by these two transcription factors but resulted from the loss of DeltaNp63, which acts as dominant-negative inhibitor of TAp63. In SCC cell lines and cancer tissues, high expression of Snail and Slug was also significantly associated with altered p63 expression. Finally, we showed that DeltaNp63 silencing reduced cell-cell adhesion and increased the migratory properties of cancer cells. These data suggest that the disruption of p63 expression induced by Snail and Slug plays a crucial role in tumor progression. Therefore, p63 and its regulating factors could constitute novel prognosis markers in patients with SCC and attractive targets for the therapeutic modulation of neoplastic cell invasiveness.
http://hdl.handle.net/2268/40469
10.2353/ajpath.2010.090804

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Herfs AJP 2010.pdfM.H. and P.H contributed equally to this study.Author postprint2.75 MBRequest copy

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