Phosphoglycerate dehydrogenase is dispensable for breast tumor maintenance and growth

Cancer cellsrely on aerobic glycolysisto maintain cell growthand proliferation via the Warburg effect. Phosphoglycerate dehydrogenase(PHDGH) catalyzes the first step of the serinebiosynthetic pathway downstream of glycolysis, which is a metabolic gatekeeperboth for macromolecular biosynthesis and serine-dependent DNA synthesis. Here, we report that PHDGH is overexpressed in many ER-negative human breast cancer celllines. PHGDH knockdown in these cells leads to a reduction of serinesynthesis and impairment of cancer cellproliferation. However, PHGDH knockdown does not affect tumor maintenance and growth in established breast cancer xenograft models, suggesting that PHGDH-dependent cancer cellgrowth may be context-dependent. Our findings suggest that other mechanisms or pathways may bypass exclusive dependence on PHGDH in established human breast cancer xenografts, indicating that PHGDH is dispensable for the growth and maintenance of tumors in vivo.