journal contribution
posted on 2023-03-31, 00:48 authored by Mathew C. Casimiro, Gabriele Di Sante, Agnese Di Rocco, Emanuele Loro, Claudia Pupo, Timothy G. Pestell, Sara Bisetto, Marco A. Velasco-Velázquez, Xuanmao Jiao, Zhiping Li, Christine M. Kusminski, Erin L. Seifert, Chenguang Wang, Daniel Ly, Bin Zheng, Che-Hung Shen, Philipp E. Scherer, Richard G. Pestell Cyclin D1 reduces cellular ATP and sensitizes cells to glucose concentration in MEF.
Funding
NIH
Breast Cancer Research Foundation
Dr. Ralph and Marian C. Falk Medical Research Trust
Pennsylvania Department of Health
American-Italian Cancer Foundation Post-doctoral Research Fellowship
History
ARTICLE 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.
