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Regulation of p63 isoforms by snail and slug transcription factors in human squamous cell carcinoma

(2010) AMERICAN JOURNAL OF PATHOLOGY. 176(4). p.1941-1949
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Abstract
TP63 is a p53-related gene that contains two alternative promoters, which give rise to transcripts that encode proteins with (TAp63) or without (dNp63) 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 dN 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 dNp63, 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 dNp63 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. (Am J Pathol 2010, 176:1941–1949; DOI: 10.2353/ajpath.2010.090804)
Keywords
(PRE)NEOPLASTIC LESIONS, EPITHELIAL-MESENCHYMAL TRANSITION, LANGERHANS CELLS, TUMOR-SUPPRESSOR, DOWN-REGULATION, UP-REGULATION, E-CADHERIN EXPRESSION, POOR-PROGNOSIS, P53 HOMOLOG, CANCER

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MLA
Herfs, Michael et al. “Regulation of P63 Isoforms by Snail and Slug Transcription Factors in Human Squamous Cell Carcinoma.” AMERICAN JOURNAL OF PATHOLOGY 176.4 (2010): 1941–1949. Print.
APA
Herfs, M., Hubert, P., Suarez-Carmona, M., Reschner, A., Saussez, S., Berx, G., Savagner, P., et al. (2010). Regulation of p63 isoforms by snail and slug transcription factors in human squamous cell carcinoma. AMERICAN JOURNAL OF PATHOLOGY, 176(4), 1941–1949.
Chicago author-date
Herfs, Michael, Pascale Hubert, Meggy Suarez-Carmona, Anca Reschner, Sven Saussez, Geert Berx, Pierre Savagner, Jacques Boniver, and Philippe Delvenne. 2010. “Regulation of P63 Isoforms by Snail and Slug Transcription Factors in Human Squamous Cell Carcinoma.” American Journal of Pathology 176 (4): 1941–1949.
Chicago author-date (all authors)
Herfs, Michael, Pascale Hubert, Meggy Suarez-Carmona, Anca Reschner, Sven Saussez, Geert Berx, Pierre Savagner, Jacques Boniver, and Philippe Delvenne. 2010. “Regulation of P63 Isoforms by Snail and Slug Transcription Factors in Human Squamous Cell Carcinoma.” American Journal of Pathology 176 (4): 1941–1949.
Vancouver
1.
Herfs M, Hubert P, Suarez-Carmona M, Reschner A, Saussez S, Berx G, et al. Regulation of p63 isoforms by snail and slug transcription factors in human squamous cell carcinoma. AMERICAN JOURNAL OF PATHOLOGY. 2010;176(4):1941–9.
IEEE
[1]
M. Herfs et al., “Regulation of p63 isoforms by snail and slug transcription factors in human squamous cell carcinoma,” AMERICAN JOURNAL OF PATHOLOGY, vol. 176, no. 4, pp. 1941–1949, 2010.
@article{936351,
  abstract     = {{TP63 is a p53-related gene that contains two alternative promoters, which give rise to transcripts that encode proteins with (TAp63) or without (dNp63) 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 dN 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 dNp63, 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 dNp63 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. (Am J Pathol 2010, 176:1941–1949; DOI: 10.2353/ajpath.2010.090804)}},
  author       = {{Herfs, Michael and Hubert, Pascale and Suarez-Carmona, Meggy and Reschner, Anca and Saussez, Sven and Berx, Geert and Savagner, Pierre and Boniver, Jacques and Delvenne, Philippe}},
  issn         = {{0002-9440}},
  journal      = {{AMERICAN JOURNAL OF PATHOLOGY}},
  keywords     = {{(PRE)NEOPLASTIC LESIONS,EPITHELIAL-MESENCHYMAL TRANSITION,LANGERHANS CELLS,TUMOR-SUPPRESSOR,DOWN-REGULATION,UP-REGULATION,E-CADHERIN EXPRESSION,POOR-PROGNOSIS,P53 HOMOLOG,CANCER}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{1941--1949}},
  title        = {{Regulation of p63 isoforms by snail and slug transcription factors in human squamous cell carcinoma}},
  url          = {{http://dx.doi.org/10.2353/ajpath.2010.090804}},
  volume       = {{176}},
  year         = {{2010}},
}

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