G6PD and cancer: First, we demonstrated that Plk1 increases PPP flux and biosynthesis from glucose catabolism; second, we established that G6PD is a direct target of Plk1 and proved that Plk1 regulates G6PD activity by interacting with and phosphorylating G6PD, which is required for the formation of active G6PD dimers; third, we found that G6PD activity is essential for Plk1-mediated cancer cell cycle progression in vitro and tumor growth in vivo.