Universität zu Köln

Robinson, Deborah J., Patel, Ankit, Purdie, Karin J., Wang, Jun ORCID: 0000-0003-2509-9599, Rizvi, Hasan, Hufbauer, Martin, Ostano, Paola, Akguel, Baki, Chiorino, Giovanna ORCID: 0000-0002-9502-6400, Harwood, Catherine A. and Bergamaschi, Daniele (2019). Epigenetic Regulation of iASPP-p63 Feedback Loop in Cutaneous Squamous Cell Carcinoma. J. Invest. Dermatol., 139 (8). S. 1658 - 1680. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1523-1747

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Abstract

Keratinocyte skin cancer, comprising cutaneous squamous (cSCC) and basal cell carcinoma, is the most common malignancy in the United Kingdom. P53 is frequently mutated in cSCC. iASPP is a key inhibitor of p53 and NF-kappa B signaling pathways and has been documented as highly expressed in several types of human cancer. We have previously identified an autoregulatory feedback loop between iASPP and p63, which is critical in epidermal homeostasis. We hypothesized a potential role for dysregulation of this axis in the pathogenesis of keratinocyte malignancies. Immunostaining of 116 cSCC clinical samples revealed increased iASPP and Delta Np63 expression, but also highlighted a significant alteration of iASPP cellular localization, with consequent deregulation of its function. Expression patterns, functionality, and gene and microRNA expression analysis were further investigated in 10 cSCC cell lines. Our data suggest that while direct effects of iASPP and p63 upon each other's expression are maintained in cSCC, epigenetic dysregulation of the feedback loop occurs at the microRNA level by a previously unreported mechanism controlling p63 expression. We demonstrate that this autoregulatory feedback loop controls cell migration in cSCC by blocking epithelial-mesenchymal transition and promoting proliferation, and provides future directions for clinical biomarker and therapeutic target discovery in cutaneous SCC.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Robinson, Deborah J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Patel, Ankit UNSPECIFIED UNSPECIFIED UNSPECIFIED Purdie, Karin J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wang, Jun UNSPECIFIED orcid.org/0000-0003-2509-9599 UNSPECIFIED Rizvi, Hasan UNSPECIFIED UNSPECIFIED UNSPECIFIED Hufbauer, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Ostano, Paola UNSPECIFIED UNSPECIFIED UNSPECIFIED Akguel, Baki UNSPECIFIED UNSPECIFIED UNSPECIFIED Chiorino, Giovanna UNSPECIFIED orcid.org/0000-0002-9502-6400 UNSPECIFIED Harwood, Catherine A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bergamaschi, Daniele UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-133863
DOI:	10.1016/j.jid.2019.01.020
Journal or Publication Title:	J. Invest. Dermatol.
Volume:	139
Number:	8
Page Range:	S. 1658 - 1680
Date:	2019
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1523-1747
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language EPITHELIAL-MESENCHYMAL TRANSITION; APOPTOSIS-STIMULATING PROTEIN; FAMILY-MEMBERS; UP-REGULATION; N-TERMINUS; P63; P53; EXPRESSION; CANCER; ISOFORM Multiple languages Dermatology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13386