Epidemiological studies have suggested that diabetes is linked to an increase risk of cancer. And high glucose levels may be a prevailing factor that contributes to the link between diabetes and cancer, but little is known about the molecular basis of this link.

     With more than four years, fortunately, a team from Fudan University published the reaearch result in Nature on July, 19. The paper named “Glucose-regulated phosphorylation of TET2 by AMPK reveals a pathway linking diabetes to cancer” reveals that metformin which is an anti-diabetic drug mediates tumor suppression.

     As we all know, the conversion of 5mC to 5hmC occurs through an oxidative reaction catalyzed by the ten-eleven translocation (TET) and the level of 5hmC can be a mark for the progress of cancer. AMPK is a key nutrient or energy sensor that is highly sensitive to glucose availability.

     In this study, the team found the molecular mechanism: increased glucose levels impede AMPK-mediated phosphorylation at serine 99, which results in the destabilization of TET2 followed by dysregulation of both 5hmC and the tumor suppressive function of TET2 in vitro and in vivo.