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Glycolysis maintains AMPK activation in sorafenib-induced Warburg effect.

ABSTRACT: 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.

SUBMITTER: Guo S

PROVIDER: S-EPMC10550717 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Glycolysis maintains AMPK activation in sorafenib-induced Warburg effect.

Guo Sijia S Zhang Chenhao C Zeng Haiou H Xia Yantao Y Weng Chenghao C Deng Yichen Y Wang Luda L Wang Huan H

Molecular metabolism 20230909

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 ...[more]

PMID: 37696356

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