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Cylindromatosis and the CYLD gene: new lessons on the molecular principles of epithelial growth control
Author(s) -
Massoumi Ramin,
Paus Ralf
Publication year - 2007
Publication title -
bioessays
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.175
H-Index - 184
eISSN - 1521-1878
pISSN - 0265-9247
DOI - 10.1002/bies.20677
Subject(s) - carcinogenesis , biology , cancer research , oncogene , gene , microbiology and biotechnology , genetics , cell cycle
Analysing cylindromatosis and the associated defects in the CYLD gene is providing novel insights into the molecular principles of epithelial growth control and carcinogenesis in, and beyond, the skin. In this review, we summarize the histopathology and histogenesis of cylindromas, and the available genetic information on patients with these skin appendage tumors. Focusing on recent data concerning the normal functions and signaling interactions of the CYLD gene product, we explain how CYLD interferes with TNF‐α or TLR‐mediated signaling as well as with JNK or NF‐κB‐dependent p65/50 signaling to limit inflammation. In addition, we delineate how CYLD interferes with activation of the proto‐oncogene Bcl 3 and with cyclin D1 expression to limit tumorigenesis, and chart how tumor growth‐promoting agents or UV light and inflammatory mediators can activate CYLD. We argue that these recent insights into CYLD function and cylindroma pathogenesis may lead to the development of novel molecular strategies for cancer prevention and treatment. BioEssays 29:1203–1214, 2007. © 2007 Wiley Periodicals, Inc.