Article (Scientific journals)
Regulation of p63 Isoforms by Snail and Slug Transcription Factors in Human Squamous Cell Carcinoma.
Herfs, Michael; Hubert, Pascale; Suarez-Carmona, Meggy et al.
2010In American Journal of Pathology, 176 (4), p. 1941-1949
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Keywords :
P63; tumorigenesis
Abstract :
[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.
Disciplines :
Oncology
Author, co-author :
Herfs, Michael ;  Université de Liège - ULiège > Doct. sc. bioméd. & pharma. (Bologne)
Hubert, Pascale  ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Suarez-Carmona, Meggy ;  Université de Liège - ULiège > 2e an. master sc. bioméd., fin. approf.
Reschner, Anca ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Saussez, S.
Berx, G.
Savagner, P.
Boniver, Jacques ;  Centre Hospitalier Universitaire de Liège - CHU > Anatomie pathologique
Delvenne, Philippe ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Language :
English
Title :
Regulation of p63 Isoforms by Snail and Slug Transcription Factors in Human Squamous Cell Carcinoma.
Publication date :
2010
Journal title :
American Journal of Pathology
ISSN :
0002-9440
eISSN :
1525-2191
Publisher :
American Society for Investigative Pathology, Bethesda, United States - Maryland
Volume :
176
Issue :
4
Pages :
1941-1949
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 26 February 2010

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