Richa Rathore, Katharine E Caldwell, Charles Schutt, Caitlyn B Brashears, Bethany C Prudner, William R Ehrhardt, Cheuk Hong Leung, Heather Lin, Najat C Daw, Hannah C Beird, Abigail Giles, Wei-Lien Wang, Alexander J Lazar, John S A Chrisinger, J Andrew Livingston, Brian A Van Tine
Osteosarcoma is the most common pediatric and adult primary malignant bone cancer. Curative regimens target the folate pathway, downstream of serine metabolism, with high-dose methotrexate. Here, the rate-limiting enzyme in the biosynthesis of serine from glucose, 3-phosphoglycerate dehydrogenase (PHGDH), is examined, and an inverse correlation between PHGDH expression and relapse-free and overall survival in osteosarcoma patients is found. PHGDH inhibition in osteosarcoma cell lines attenuated cellular proliferation without causing cell death, prompting a robust metabolic analysis to characterize pro-survival compensation...
January 26, 2021: Cell Reports