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Publication : Cyclin D1 Restrains Oncogene-Induced Autophagy by Regulating the AMPK-LKB1 Signaling Axis.

First Author  Casimiro MC Year  2017
Journal  Cancer Res Volume  77
Issue  13 Pages  3391-3405
PubMed ID  28522753 Mgi Jnum  J:243114
Mgi Id  MGI:5907744 Doi  10.1158/0008-5472.CAN-16-0425
Citation  Casimiro MC, et al. (2017) Cyclin D1 Restrains Oncogene-Induced Autophagy by Regulating the AMPK-LKB1 Signaling Axis. Cancer Res 77(13):3391-3405
abstractText  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. (c)2017 AACR.
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