Heuser, S., Hufbauer, M., Steiger, J., Marshall, J., Sterner-Kock, A., Mauch, C., Zigrino, P. and Akguel, B. (2016). The fibronectin/alpha 3 beta 1 integrin axis serves as molecular basis for keratinocyte invasion induced by beta HPV. Oncogene, 35 (34). S. 4529 - 4540. LONDON: NATURE PUBLISHING GROUP. ISSN 1476-5594
Full text not available from this repository.Abstract
Organ-transplant-recipients exhibit cancerization of the skin from which multiple human papillomavirus (HPV)-positive squamous cell carcinomas (SCCs) arise. However, the molecular basis for HPV-induced invasion of skin keratinocytes is not known. We generated a transgenic mouse model expressing the E7 oncoprotein of HPV8 in the murine epidermis under the control of the keratin-14 promoter and showed that E7 is carcinogenic in mice. We further showed that both, the E7-expressing keratinocyte and mesenchymal components of the extracellular matrix as critical in eliciting the invasive behavior. E7 expression in basal keratinocytes, grown on fibronectin, led to epithelial-mesenchymal transition mediated by a cadherin switch. E7-positive keratinocytes displayed enhanced EDA-fibronectin expression and secretion and stimulated dermal fibroblasts to express EDA-fibronectin. Deposition of fibronectin was also detected in the peritumoral stroma of HPV8-positive skin SCC. When grown on fibronectin, E7-positive keratinocytes, in particular stem cell-like cells, exhibited increased cell surface levels of the alpha 3-integrin chain. Functional blocking confirmed alpha 3 as a critical molecule sufficient to induce E7-mediated invasion. This mechanistic link is further supported by expression of an E7-mutant, impaired in targeting alpha 3 to the cell surface. These findings highlight the importance of epithelial-extracellular matrix interaction required for keratinocyte invasion and provide further mechanistic evidence for a role of HPV in skin carcinogenesis.
Item Type: | Journal Article | ||||||||||||||||||||||||||||||||||||
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URN: | urn:nbn:de:hbz:38-269100 | ||||||||||||||||||||||||||||||||||||
DOI: | 10.1038/onc.2015.512 | ||||||||||||||||||||||||||||||||||||
Journal or Publication Title: | Oncogene | ||||||||||||||||||||||||||||||||||||
Volume: | 35 | ||||||||||||||||||||||||||||||||||||
Number: | 34 | ||||||||||||||||||||||||||||||||||||
Page Range: | S. 4529 - 4540 | ||||||||||||||||||||||||||||||||||||
Date: | 2016 | ||||||||||||||||||||||||||||||||||||
Publisher: | NATURE PUBLISHING GROUP | ||||||||||||||||||||||||||||||||||||
Place of Publication: | LONDON | ||||||||||||||||||||||||||||||||||||
ISSN: | 1476-5594 | ||||||||||||||||||||||||||||||||||||
Language: | English | ||||||||||||||||||||||||||||||||||||
Faculty: | Unspecified | ||||||||||||||||||||||||||||||||||||
Divisions: | Unspecified | ||||||||||||||||||||||||||||||||||||
Subjects: | no entry | ||||||||||||||||||||||||||||||||||||
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Refereed: | Yes | ||||||||||||||||||||||||||||||||||||
URI: | http://kups.ub.uni-koeln.de/id/eprint/26910 |
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