Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.30.228759v1?rss=1 Authors: Jacquier, V., Gitenay, D., Fritsch, S., Linares, L. K., Bonnet, S., Jalaguier, S., Cavaillès, V., Teyssier, C. Abstract: Cancer cells with uncontrolled proliferation preferentially depend on glycolysis to grow, even in the presence of oxygen. Cancer cell proliferation is sustained by the production of glycolytic intermediates, which are diverted into the pentose phosphate pathway. The transcriptional co-regulator RIP140 represses the activity of transcription factors that drive cell proliferation and metabolism, especially glycolysis. However, it is still unknown whether RIP140 is involved in cancer-associated glycolysis deregulation, and whether this involvement could impact tumor cell proliferation. Here we use cell proliferation and metabolic assays to demonstrate that RIP140-deficiency causes a glycolysis-dependent increase in breast tumor growth. RIP140 inhibits the expression of the glucose transporter GLUT3 and of the Glucose-6-Phosphate Dehydrogenase G6PD, the first enzyme of the pentose phosphate pathway. RIP140 thus impacts both this pathway and glycolysis to block cell proliferation. We further demonstrate that RIP140 and p53 jointly inhibit the transcription of the GLUT3 promoter, induced by the hypoxia inducible factor HIF-2&. Overall, our data establish RIP140 as a critical modulator of the p53/HIF cross-talk that controls cancer glycolysis. Copy rights belong to original authors. Visit the link for more info