RIP140 inhibits glycolysis-dependent proliferation of breast cancer cells by regulating GLUT3 expression through transcriptional crosstalk between hypoxia induced factor and p53
| Autor: | Vincent Cavaillès, Sandrine Bonnet, Laetitia K. Linares, Catherine Teyssier, Valentin Jacquier, Delphine Gitenay, Balazs Gyorffy, Samuel Fritsch, Stéphan Jalaguier |
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| Přispěvatelé: | Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Semmelweis University [Budapest], Herrada, Anthony |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
p53
Breast Neoplasms [SDV.CAN]Life Sciences [q-bio]/Cancer Pentose phosphate pathway Cellular and Molecular Neuroscience Breast cancer MESH: Hypoxia [SDV.CAN] Life Sciences [q-bio]/Cancer Cancer cell metabolism MESH: Cell Proliferation [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] MESH: Basic Helix-Loop-Helix Transcription Factors Basic Helix-Loop-Helix Transcription Factors Transcription factors Humans HIF Glycolysis MESH: Nuclear Receptor Interacting Protein 1 Hypoxia MESH: Tumor Suppressor Protein p53 Molecular Biology Transcription factor Cell Proliferation Pharmacology MESH: Humans biology Glucose Transporter Type 3 Chemistry Cell growth Cell Biology Metabolism Cell biology Nuclear Receptor Interacting Protein 1 Hypoxia-inducible factors RIP140 Cancer cell MESH: Glycolysis biology.protein Molecular Medicine [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] Female MESH: Glucose Transporter Type 3 Tumor Suppressor Protein p53 GLUT3 MESH: Female MESH: Breast Neoplasms |
| Zdroj: | Cellular and Molecular Life Sciences Cellular and Molecular Life Sciences, Springer Verlag, 2022, 79 (5), pp.270. ⟨10.1007/s00018-022-04277-3⟩ |
| ISSN: | 1420-682X 1420-9071 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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