Universität zu Köln

De Craene, B., Denecker, G., Vermassen, P., Taminau, J., Mauch, C., Derore, A., Jonkers, J., Fuchs, E. and Berx, G. (2014). Epidermal Snail expression drives skin cancer initiation and progression through enhanced cytoprotection, epidermal stem/progenitor cell expansion and enhanced metastatic potential. Cell Death Differ., 21 (2). S. 310 - 321. LONDON: NATURE PUBLISHING GROUP. ISSN 1476-5403

Full text not available from this repository.

Abstract

Expression of the EMT-inducing transcription factor Snail is enhanced in different human cancers. To investigate the in vivo role of Snail during progression of epithelial cancer, we used a mouse model with skin-specific overexpression of Snail. Snail transgenic mice spontaneously developed distinct histological subtypes of skin cancer, such as basal cell carcinoma, squamous cell carcinoma and sebaceous gland carcinoma. Development of sebaceous gland carcinomas strongly correlated with the direct and complete repression of Blimp-1, a central regulator of sebocyte homeostasis. Snail expression in keratinocyte stem cells significantly promotes their proliferation associated with an activated FoxM1 gene expression signature, resulting in a larger pool of Mts24-marked progenitor cells. Furthermore, primary keratinocytes expressing Snail showed increased survival and strong resistance to genotoxic stress. Snail expression in a skin-specific p53-null background resulted in accelerated formation of spontaneous tumours and enhanced metastasis. Our data demonstrate that in vivo expression of Snail results in de novo epithelial carcinogenesis by allowing enhanced survival, expansion of the cancer stem cell pool with accumulated DNA damage, a block in terminal differentiation and increased proliferation rates of tumour-initiating cells.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code De Craene, B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Denecker, G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Vermassen, P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Taminau, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mauch, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Derore, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Jonkers, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fuchs, E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Berx, G. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-447370
DOI:	10.1038/cdd.2013.148
Journal or Publication Title:	Cell Death Differ.
Volume:	21
Number:	2
Page Range:	S. 310 - 321
Date:	2014
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	1476-5403
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language EPITHELIAL-MESENCHYMAL TRANSITION; TRANSCRIPTION FACTOR SNAIL; STEM-CELLS; E-CADHERIN; HAIR FOLLICLE; TUMOR RECURRENCE; REPRESSOR SNAIL; DIFFERENTIATION; KERATINOCYTES; PROTEIN Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/44737