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

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cam.issuedOnline2018-10-18
dc.contributor.authorSmirnov, Artem
dc.contributor.authorLena, Anna Maria
dc.contributor.authorCappello, Angela
dc.contributor.authorPanatta, Emanuele
dc.contributor.authorAnemona, Lucia
dc.contributor.authorBischetti, Simone
dc.contributor.authorAnnicchiarico-Petruzzelli, Margherita
dc.contributor.authorMauriello, Alessandro
dc.contributor.authorMelino, Gerry
dc.contributor.authorCandi, Eleonora
dc.contributor.orcidSmirnov, Artem [0000-0002-1575-8725]
dc.contributor.orcidMauriello, Alessandro [0000-0002-7351-5676]
dc.date.accessioned2018-11-21T00:30:49Z
dc.date.available2018-11-21T00:30:49Z
dc.date.issued2019-03
dc.description.abstractDevelopment 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.
dc.description.sponsorshipThis 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).
dc.format.mediumPrint-Electronic
dc.identifier.doi10.17863/CAM.32875
dc.identifier.eissn1476-5594
dc.identifier.issn0950-9232
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/285517
dc.languageeng
dc.language.isoeng
dc.publisherSpringer Science and Business Media LLC
dc.publisher.urlhttp://dx.doi.org/10.1038/s41388-018-0509-4
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectAntigens, CD
dc.subjectCadherins
dc.subjectCarcinoma, Squamous Cell
dc.subjectCell Adhesion
dc.subjectCell Differentiation
dc.subjectCells, Cultured
dc.subjectCytoskeletal Proteins
dc.subjectDown-Regulation
dc.subjectEnhancer Elements, Genetic
dc.subjectEpithelial Cells
dc.subjectGene Expression Profiling
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectHumans
dc.subjectKeratinocytes
dc.subjectLIM Domain Proteins
dc.subjectModels, Biological
dc.subjectSequence Analysis, RNA
dc.subjectTranscription Factors
dc.subjectTumor Suppressor Proteins
dc.titleZNF185 is a p63 target gene critical for epidermal differentiation and squamous cell carcinoma development.
dc.typeArticle
dcterms.dateAccepted2018-08-17
prism.endingPage1638
prism.issueIdentifier10
prism.publicationDate2019
prism.publicationNameOncogene
prism.startingPage1625
prism.volume38
rioxxterms.licenseref.startdate2019-03
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1038/s41388-018-0509-4

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