RT Journal Article SR Electronic T1 RIP140 inhibits glycolysis-dependent proliferation of breast cancer cells by regulating GLUT3 expression through transcriptional crosstalk between hypoxia induced factor and p53 JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.07.30.228759 DO 10.1101/2020.07.30.228759 A1 Valentin Jacquier A1 Delphine Gitenay A1 Samuel Fritsch A1 Sandrine Bonnet A1 Balázs Győrffy A1 Stéphan Jalaguier A1 Laetitia K. Linares A1 Vincent Cavaillès A1 Catherine Teyssier YR 2022 UL http://biorxiv.org/content/early/2022/02/02/2020.07.30.228759.abstract AB Cancer cells with uncontrolled proliferation preferentially depend on glycolysis to grow, even in the presence of oxygen. The transcriptional co-regulator RIP140 represses the activity of transcription factors that drive cell proliferation and metabolism and plays a role in mammary tumorigenesis. Here we use cell proliferation and metabolic assays to demonstrate that RIP140-deficiency causes a glycolysis-dependent increase in breast tumor growth. We further demonstrate that RIP140 reduces the transcription of the glucose transporter GLUT3 gene, by inhibiting the transcriptional activity of hypoxia inducible factor HIF-2α in cooperation with p53. Interestingly, RIP140 expression was significantly associated with good prognosis only for breast cancer patients with tumors expressing low GLUT3, low HIF-2α and high p53, thus confirming the mechanism of RIP140 anti-tumor activity provided by our experimental data. Overall, our work establishes RIP140 as a critical modulator of the p53/HIF cross-talk to inhibit breast cancer cell glycolysis and proliferation.Competing Interest StatementThe authors have declared no competing interest.