Serine Biosynthesis Is a Metabolic Vulnerability in IDH2-Driven Breast Cancer Progression.

ABSTRACT: Cancer-specific metabolic phenotypes and their vulnerabilities represent a viable area of cancer research. In this study, we explored the association of breast cancer subtypes with different metabolic phenotypes and identified isocitrate dehydrogenase 2 (IDH2) as a key player in triple-negative breast cancer (TNBC) and HER2. Functional assays combined with mass spectrometry-based analyses revealed the oncogenic role of IDH2 in cell proliferation, anchorage-independent growth, glycolysis, mitochondrial respiration, and antioxidant defense. Genome-scale metabolic modeling identified phosphoglycerate dehydrogenase (PHGDH) and phosphoserine aminotransferase (PSAT1) as the synthetic dosage lethal (SDL) partners of IDH2. In agreement, CRISPR-Cas9 knockout of PHGDH and PSAT1 showed the essentiali

SUBMITTER: Barnabas GD 

PROVIDER: S-EPMC9216326 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature