Axl promotes cutaneous squamous cell carcinoma survival through negative regulation of pro-apoptotic Bcl-2 family members

Article


Papadakis, E., Cichoń, M., Vyas, J., Patel, N., Ghali, L., Cerio, R., Storey, A. and O'Toole, E. 2011. Axl promotes cutaneous squamous cell carcinoma survival through negative regulation of pro-apoptotic Bcl-2 family members. Journal of investigative dermatology. 131 (2), pp. 509-517. https://doi.org/10.1038/jid.2010.326
TypeArticle
TitleAxl promotes cutaneous squamous cell carcinoma survival through negative regulation of pro-apoptotic Bcl-2 family members
AuthorsPapadakis, E., Cichoń, M., Vyas, J., Patel, N., Ghali, L., Cerio, R., Storey, A. and O'Toole, E.
Abstract

Expression of Axl, a receptor tyrosine kinase, is increased in cutaneous squamous cell carcinoma (SCC). Examination of a series of cutaneous SCC tumors revealed positive phospho-Akt (P-Akt) staining accompanied by weak TUNEL staining in Axl-positive tumors, suggesting an anti-apoptotic role for Axl in SCC survival. The role of Axl in UV-induced apoptosis was investigated in a cutaneous SCC cell line using retroviral short hairpin RNA sequences enabling stable Axl knock-down. We show that, although Axl knock-down has no effect on cell proliferation, it sensitizes cells to UV-induced apoptosis through increased activation of the pro-apoptotic protein Bad, a change in the conformation of Bax and Bak, release of cytochrome c into the cytosol, and activation of caspases. These events are accompanied by faster Akt dephosphorylation in UV-treated Axl knock-down cells and correlate with the degree of Axl knock-down. Treatment with the pan-caspase inhibitor zVAD-fmk partially rescued cells from UV-induced apoptosis but did not affect Bid cleavage or cytochrome c release, suggesting that cells die via the mitochondrial-mediated pathway. Thus, Axl confers resistance of SCC cells to apoptosis and displays potential as a target for therapeutic intervention in cutaneous SCC.

Research GroupBiomarkers for Cancer group
LanguageEnglish
PublisherNature Publishing Group
JournalJournal of investigative dermatology
ISSN0022-202X
Publication dates
PrintFeb 2011
Publication process dates
Deposited02 Jul 2013
Output statusPublished
Digital Object Identifier (DOI)https://doi.org/10.1038/jid.2010.326
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