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Cancer Lett. 2014 Mar 28;344(2):272-81. doi: 10.1016/j.canlet.2013.11.005. Epub 2013 Nov 19.

Chronic mTOR activation promotes cell survival in Merkel cell carcinoma.

Author information

  • 1Department of Dermatology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States; Cancer Center Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China.
  • 2College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States.
  • 3Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States.
  • 4Department of Dermatology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States.
  • 5University of South Florida, College of Medicine, Tampa, FL, United States.
  • 6Department of Otolaryngology-Head and Neck Surgery, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States.
  • 7Department of Internal Medicine, Division of Dermatology, Washington University School of Medicine in St. Louis, St. Louis 63110, United States.
  • 8Department of Dermatology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States. Electronic address: LGao@uams.edu.

Abstract

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.

KEYWORDS:

Autophagy; Cell death; Merkel cell carcinoma; mTOR inhibitor; mTOR pathway

PMID:
24262658
[PubMed - indexed for MEDLINE]
PMCID:
PMC4080622
Free PMC Article
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