HIF1A and nonpapillary renal cell carcinoma: Although the activation of AMPK by metformin has been shown to decrease the expression of HIF-1α and mTOR activation in some cancers and in diabetic rat kidneys [23,24,25], comprehensive signaling pathways exerted by metformin to inhibit cell proliferation, cell cycle arrest and apoptosis in ccRCC are yet to be thoroughly investigated.