Development and maintenance of healthy stratified epithelia require the coordination of complex transcriptional programmes. The transcription factor p63, a member of the p53 family, plays a crucial role in epithelial development and homeostasis. Analysis of the p63-dependent transcriptome indicated that one important aspect of p63 functions in epithelial development is the regulation of cell-cell and cell-matrix adhesion programmes. However, limited knowledge exists on the relevant cell-cell adhesion molecules involved in physiological epithelial formation. Similarly, limited data are available to understand if deregulation of the cell-cell adhesion programme is important in tumour formation. Here, using the epidermis as an experimental model with the RNA sequencing approach, we identify a novel p63-regulated gene induced during differentiation, ZNF185. ZNF185 is an actin-cytoskeleton-associated Lin-l 1, Isl-1 and Mec-3 (LIM) domain containing protein, whose function is poorly known. We found that p63 binds to a specific enhancer region, promoting its expression to sustain epithelial differentiation. ZNF185 silencing strongly impaired keratinocyte differentiation according to gene array analysis. ZNF185 is detected at the cell-cell periphery where it physically interacts with E-cadherin, indicating that it is important to maintain epithelial integrity beyond its pro-differentiation role. Interestingly, poorly differentiated, including head and neck, cervical and oesophageal, squamous cell carcinomas display loss of ZNF185 expression. Together, these studies reinforce that p63 is a crucial gene for maintaining epithelial tissue integrity and support the deregulation of the cell-cell adhesion programme,which plays a critical role in carcinoma development.

Smirnov, A., Lena, A.m., Cappello, A., Panatta, E., Anemona, L., Bischetti, S., et al. (2019). ZNF185 is a p63 target gene critical for epidermal differentiation and squamous cell carcinoma development. ONCOGENE, 38(10), 1625-1638 [10.1038/s41388-018-0509-4].

ZNF185 is a p63 target gene critical for epidermal differentiation and squamous cell carcinoma development

Smirnov, Artem;Lena, Anna Maria;Anemona, Lucia;Mauriello, Alessandro;Melino, Gennaro
;
Candi, Eleonora
2019-01-01

Abstract

Development and maintenance of healthy stratified epithelia require the coordination of complex transcriptional programmes. The transcription factor p63, a member of the p53 family, plays a crucial role in epithelial development and homeostasis. Analysis of the p63-dependent transcriptome indicated that one important aspect of p63 functions in epithelial development is the regulation of cell-cell and cell-matrix adhesion programmes. However, limited knowledge exists on the relevant cell-cell adhesion molecules involved in physiological epithelial formation. Similarly, limited data are available to understand if deregulation of the cell-cell adhesion programme is important in tumour formation. Here, using the epidermis as an experimental model with the RNA sequencing approach, we identify a novel p63-regulated gene induced during differentiation, ZNF185. ZNF185 is an actin-cytoskeleton-associated Lin-l 1, Isl-1 and Mec-3 (LIM) domain containing protein, whose function is poorly known. We found that p63 binds to a specific enhancer region, promoting its expression to sustain epithelial differentiation. ZNF185 silencing strongly impaired keratinocyte differentiation according to gene array analysis. ZNF185 is detected at the cell-cell periphery where it physically interacts with E-cadherin, indicating that it is important to maintain epithelial integrity beyond its pro-differentiation role. Interestingly, poorly differentiated, including head and neck, cervical and oesophageal, squamous cell carcinomas display loss of ZNF185 expression. Together, these studies reinforce that p63 is a crucial gene for maintaining epithelial tissue integrity and support the deregulation of the cell-cell adhesion programme,which plays a critical role in carcinoma development.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/10
Settore MED/08
English
Smirnov, A., Lena, A.m., Cappello, A., Panatta, E., Anemona, L., Bischetti, S., et al. (2019). ZNF185 is a p63 target gene critical for epidermal differentiation and squamous cell carcinoma development. ONCOGENE, 38(10), 1625-1638 [10.1038/s41388-018-0509-4].
Smirnov, A; Lena, Am; Cappello, A; Panatta, E; Anemona, L; Bischetti, S; Annicchiarico-Petruzzelli, M; Mauriello, A; Melino, G; Candi, E
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/238776
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