BRAFV600E in Colorectal Cancer Reduces Sensitivity to Oxidative Stress and Promotes Site-Specific Metastasis by Stimulating Glutathione Synthesis

BRAFV600E tumors and PDOs express high levels of glutamate-cysteine ligase (GCL), the rate-limiting enzyme in glutathione synthesis. Deletion of GCL in BRAFV600E PDOs strongly reduced their capacity to form distant liver and lung metastases but did not affect peritoneal metastasis outgrowth.