The Role of Phosphoglycerate Dehydrogenase in Cell Proliferation and Tumor Progression

The study explored the role of phosphoglycerate dehydrogenase (PHGDH) in cancer cell proliferation and tumor progression. PHGDH, which catalyzes the first step in the serine biosynthesis pathway, was found to be amplified in human cancers, and its expression was crucial for the proliferation of PHGDH-amplified cells. The research suggested that PHGDH might be an important source of NADPH, a reductive currency for biosynthesis and redox maintenance. Experiments with mutant PHGDH enzymes indicated that the enzyme's ability to produce NADPH was necessary for cell proliferation. Additionally, overexpression of PHGDH in a transgenic mouse model led to abnormal melanin granules in hair follicles and accelerated tumor growth in a melanoma model. The findings identified PHGDH as a metabolic enzyme that, when overexpressed, could promote cancer initiation and progression, highlighting its significance in cancer cell metabolism and tumorigenesis.