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Inhibition of glutaminolysis inhibits cell growth via down-regulating mTORC1 signaling in lung squamous cell carcinoma. : mTORC1

by XuLu Ye

Institution: Niigata University /
Department:
Degree:
Year: 2017
Keywords: Lung squamous cell carcinoma; molecular targeted therapy; glutaminolysis; glutaminase; BPTES; mTORC1
Posted: 2/1/2018 12:00:00 AM
Record ID: 2157634
Full text PDF: http://hdl.handle.net/10191/47578


Abstract

: . : 4247. : 725. : 29323 Anticancer Research 36(11) 6021-6029(2016) Background/Aim: Inhibition of glutaminolysis has been reported as a promising therapeutic strategy to target several solid carcinomas. We aimed to investigate the effects of glutaminolysis on cell proliferation in lung squamous cell carcinoma cell lines and to explore the potential of targeting glutaminolysis as an anticancer strategy. Materials and Methods: Glutamine (Gln) dependence was assessed in six lung squamous cell carcinoma cell lines. Cell proliferation, mammalian target of rapamycin complex 1 (mTORC1) activity and the induction of autophagy were assessed after inhibition of glutaminolysis via Gln depletion or glutaminase (GLS) inhibition. Results: Five of six lung squamous cell carcinoma cell lines exhibited glutamine-dependence. The extent of dependence was correlated with the mRNA levels of GLS1/GLS2. Inhibition of glutaminolysis inhibited cell proliferation by down-regulating of mTORC1 signaling and inducing autophagy in Gln-dependent lung squamous cell carcinoma cell lines. Conclusion: Targeting glutaminolysis may represent a potential therapeutic strategy for the treatment of Gln-dependent lung squamous cell carcinomas.

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