PHGDH Acts as an Oncogenic Accelerator by Activating the c-MYC/CDK2 Axis to Drive Cell Cycle Progression in Endometrial Cancer

Endometrial cancer (EC) is one of the most prevalent gynecological tumors with rising incidence and mortality rates ^[1] . Phosphoglycerate dehydrogenase (PHGDH), a key enzyme in serine biosynthesis, is closely related to the progression of various cancers, yet its role in EC pathogenesis remains poorly understood. Immunohistochemistry was used to detect the PHGDH expression and its correlation with clinical indicators in EC and normal endometrial tissues and to analyze its correlation with clinicopathological parameters. We explored the role of PHGDH in the progression of EC through in vitro and in vivo assays. Analysis of public databases and clinical specimens revealed that PHGDH expression is significantly elevated in EC tissues compared to normal endometrium, and high PHGDH levels correlate with poor patient prognosis. In vitro studies demonstrated that PHGDH promotes the proliferation of EC cells. In vivo assays showed that the PHGDH inhibitor NCT-503 effectively suppresses tumor growth, exhibiting selective efficacy across different cell lines. Transcriptome sequencing indicated that PHGDH influences multiple biological processes, including cell cycle. Mechanistically, PHGDH was found to regulate the cell cycle by modulating the PHGDH/c-MYC/CyclinA2/CDK2 axis. Functionally, PHGDH drives cancer progression through alterations in cell cycle regulation, whereas its pharmacological inhibition can counteract these effects. PHGDH exerts a tumor-promoting effect in endometrial cancer and represents a promising therapeutic target for inhibiting EC progression.