Journal
CANCER LETTERS
Volume 344, Issue 2, Pages 272-281Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2013.11.005
Keywords
Merkel cell carcinoma; mTOR pathway; Autophagy; Cell death; mTOR inhibitor
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Funding
- Translational Research Institute (TRI) through the NIH National Center for Research Resources [UL1TR000039, KL2TR000063]
- National Center for Advancing Translational Sciences
- Department of Dermatology
- Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences
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Merkel cell carcinoma (MCC) is an aggressive skin cancer with rising incidence. In this study, we demonstrate that mTOR activation and suppressed autophagy is common in MCCs. mTOR inhibition in two primary human MCC cell lines induces autophagy and cell death that is independent of caspase activation but can be attenuated by autophagy inhibition. This is the first study to evaluate mTOR and autophagy in MCC. Our data suggests a potential role of autophagic cell death upon mTOR inhibition and thus uncovers a previously underappreciated role of mTOR signaling and cell survival, and merits further studies for potential therapeutic targets. Published by Elsevier Ireland Ltd.
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