摘要：SummaryDysregulated glycolysis, including the cancerous Warburg effect, is closely involved in pathological mechanisms of diseased states. Among glycolytic enzymes, phosphoglycerate mutase (PGAM) has been known to exert certain physiological impactin vitro, whereas its regulatory role on glycolysis remains unclear. Here, we identified that PGAM plays a key role in regulating glycolysis in cancer cells but not in standard cells. Cancer-prone phenotype by PGAM overexpressionin vivowas associated with upregulated glycolytic features. PGAM interacts and cooperates with Chk1 to regulate the enhanced glycolysis in cancer cells, especially under oncogenic Ras expressing conditions. Genetic or chemical interference of the PGAM-Chk1 interaction, with intact PGAM activity, abrogated the maintenance of cancerous enhanced glycolysis. Thus, the nonenzymatic function of PGAM is essential for the Warburg effect that accompanies cancerous proliferation.Graphical AbstractDisplay OmittedHighlights•PGAM cooperates with Chk1 kinase to boost glycolysis in a non-enzymatic manner•PGAM interacts with Chk1 in cancer with oncogenic Ras but not in standard cells•Chemical and genetical interference with PGAM-Chk1 axis abrogates the Warburg effectGlycobiology; Molecular Biology; Cancer
