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Atg7 inhibits Warburg effect by suppressing PKM2 phosphorylation resulting reduced epithelial-mesenchymal transition.

Yanling Feng | Jingwei Liu | Wendong Guo | Yi Guan | Hongde Xu | Qiqiang Guo | Xiaoyu Song | Fei Yi | Ting Liu | Wenyu Zhang | Xiang Dong | Longyue L Cao | Brian P O'Rourke | Liu Cao
International journal of biological sciences | 2018

Metabolic reprogramming is a distinct hallmark in tumorigenesis. Autophagy can rewire cell metabolism by regulating intracellular homeostasis. Warburg effect is a specific energy metabolic process that allows tumor cells to metabolize glucose via glycolysis into lactate even in the presence of oxygen. Although both autophagy and Warburg effect are involved in the stress response to energy crisis in tumor cells, their molecular relationship has remained largely elusive. We found that Atg7, a key molecule involved in autophagy, inhibits the Warburg effect. Mechanistically, Atg7 binds PKM2 and prevents its Tyr-105 phosphorylation by FGFR1. Furthermore, the hyperphosphorylation of PKM2 and its induced Warburg effect due to Atg7 deficiency promote epithelial-mesenchymal transition (EMT). Conversely, overexpression of Atg7 inhibits PKM2 phosphorylation and the Warburg effect, thereby inhibiting EMT of tumor cells. Our work reveals a molecular link between Atg7 and the Warburg effect, which may provide insight into novel strategies for cancer treatment.

Pubmed ID: 29910687

Associated grants

  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM007288

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