| Literature DB >> 28522753 |
Mathew C Casimiro1,2, Gabriele Di Sante1,2, Agnese Di Rocco1,2, Emanuele Loro3, Claudia Pupo3, Timothy G Pestell3, Sara Bisetto3, Marco A Velasco-Velázquez3, Xuanmao Jiao3, Zhiping Li3, Christine M Kusminski4, Erin L Seifert5, Chenguang Wang3, Daniel Ly3, Bin Zheng6, Che-Hung Shen6, Philipp E Scherer4, Richard G Pestell7,2.
Abstract
Autophagy activated after DNA damage or other stresses mitigates cellular damage by removing damaged proteins, lipids, and organelles. Activation of the master metabolic kinase AMPK enhances autophagy. Here we report that cyclin D1 restrains autophagy by modulating the activation of AMPK. In cell models of human breast cancer or in a cyclin D1-deficient model, we observed a cyclin D1-mediated reduction in AMPK activation. Mechanistic investigations showed that cyclin D1 inhibited mitochondrial function, promoted glycolysis, and reduced activation of AMPK (pT172), possibly through a mechanism that involves cyclin D1-Cdk4/Cdk6 phosphorylation of LKB1. Our findings suggest how AMPK activation by cyclin D1 may couple cell proliferation to energy homeostasis. Cancer Res; 77(13); 3391-405. ©2017 AACR. ©2017 American Association for Cancer Research.Entities:
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Year: 2017 PMID： 28522753 PMCID： PMC5705201 DOI： 10.1158/0008-5472.CAN-16-0425
Source DB: PubMed Journal: Cancer Res ISSN： 0008-5472 Impact factor: 12.701