Int J Biol Sci 2018; 14(7):775-783. doi:10.7150/ijbs.26077
Atg7 inhibits Warburg effect by suppressing PKM2 phosphorylation resulting reduced epithelial-mesenchymal transition
1. Key Laboratory of Medical Cell Biology, Ministry of Education; Institute of Translational Medicine, China Medical University; Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, Shenyang, Liaoning Province, China
2. Wilf Family Cardiovascular Research Institute, Department of Medicine (Cardiology), Albert Einstein College of Medicine, Bronx, New York 10461, USA
3. Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, New York 10461, USA
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.
Keywords: Autophagy, Warburg effect, Atg7, PKM2, EMT, Metabolic reprogramming
Feng Y, Liu J, Guo W, Guan Y, Xu H, Guo Q, Song X, Yi F, Liu T, Zhang W, Dong X, Cao LL, O'Rourke BP, Cao L. Atg7 inhibits Warburg effect by suppressing PKM2 phosphorylation resulting reduced epithelial-mesenchymal transition. Int J Biol Sci 2018; 14(7):775-783. doi:10.7150/ijbs.26077. Available from http://www.ijbs.com/v14p0775.htm