Glycolysis maintains AMPK activation in sorafenib-induced Warburg effect

作者：Sijia Guo, Chenhao Zhang, Haiou Zeng, Yantao Xia, Chenghao Weng, Yichen Deng, Luda Wang, Huan Wang · 发表于：Molecular Metabolism · 年份：2023 · DOI：10.1016/j.molmet.2023.101796 · 被引用次数：16 · 研究领域：Metabolism, Diabetes, and Cancer、Cancer, Hypoxia, and Metabolism、Pancreatic function and diabetes

Hepatocellular carcinoma (HCC) is the second deadly cancer in the world and still lacks curative treatment. Aerobic glycolysis, or Warburg effect, is a major resistance mechanism induced by first-line treatment of HCC, sorafenib, and is regulated by the master regulator of metabolism, AMPK. Activation of AMPK is required for resistance; however, activation dynamics of AMPK and its regulation is rarely studied. Engineering cells to express an AMPK activity biosensor, we monitor AMPK activation in single HCC cells in a high throughput manner during sorafenib-induced drug resistance. Sorafenib induces transient activation of AMPK, duration of which is dependent on glucose. Inhibiting glycolysis shortens AMPK activation; whereas increasing glycolysis increases its activation duration. Our data highlight that activation duration of AMPK is important for cancer evasion of therapeutic treatment and glycolysis is a key regulator of activation duration of AMPK.