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

Lena, Anna Maria 
Cappello, Angela 
Panatta, Emanuele 
Anemona, Lucia 

Thumbnail Image
Change log

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.

Publication Date
Online Publication Date
Acceptance Date
Antigens, CD, Cadherins, Carcinoma, Squamous Cell, Cell Adhesion, Cell Differentiation, Cells, Cultured, Cytoskeletal Proteins, Down-Regulation, Enhancer Elements, Genetic, Epithelial Cells, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Keratinocytes, LIM Domain Proteins, Models, Biological, Sequence Analysis, RNA, Transcription Factors, Tumor Suppressor Proteins
Journal Title
Journal ISSN
Volume Title
Springer Science and Business Media LLC
This work has been partially supported by AIRC Grant IG-15653 to GM. This work has been mainly supported by IDI-IRCCS (RC to EC and GM) and RF-2016-02362541 (to EC).