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Chronic mTOR activation promotes cell survival in Merkel cell carcinoma.


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.

SUBMITTER: Lin Z 

PROVIDER: S-EPMC4080622 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Chronic mTOR activation promotes cell survival in Merkel cell carcinoma.

Lin Zhenyu Z   McDermott Amelia A   Shao Lijian L   Kannan Aarthi A   Morgan Michael M   Stack Brendan C BC   Moreno Mauricio M   Davis Daniel A DA   Cornelius Lynn A LA   Gao Ling L  

Cancer letters 20131119 2


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 thu  ...[more]

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