Malignant transformation by oncogenic K-ras requires IDH2-mediated reductive carboxylation to promote glutamine utilization

[摘要] Oncogenic K-ras mutation plays a major role in malignant transformation and induces significant alterationsin cancer cell metabolism [1–4]. However, the majormolecular players mediating metabolic alterations during K-ras-driven cancer development remain elusive. Theobservations that tumorigenesis often requires multiplehits suggest that K-ras mutation likely needs the coordination of other molecular events that enable adaptive cellularmetabolism for a full malignant transformation. Based onour previous study on the impact of K-ras on mitochondrialmetabolism [1, 5] and our recent findings that mitochondrial isocitrate dehydrogenase 2 (IDH2) could promote the“reverse” flow of the tricarboxylic acid (TCA) cycle fromα-KG to isocitrate and enhance the survival and proliferation of acute myeloid leukemia cells [6], we investigatedthe potential role of IDH2 in metabolic adaptation duringK-ras-driven tumorigenesis.

[学科分类] 社会科学、人文和艺术（综合）