PHGDH promotes esophageal squamous cell carcinoma progression via Wnt/β-catenin pathway

Abstract

PurposeEsophageal squamous carcinoma (ESCC) with a high incidence in China, lacks effective therapeutic targets. Phosphoglycerate dehydrogenase (PHGDH) is a key enzyme in serine biosynthesis. However, the biological role of PHGDH in ESCC has not been revealed. MethodsThe expression of PHGDH in ESCC was investigated by UALCAN. The relationship between PHGDH expression and its prognostic value was analyzed by Kaplan-Meier and univariate Cox regression. Further, the potential functions of PHGDH involved in ESCC were explored through DAVID database and GSEA software. In addition, the expression of PHGDH was verified in ESCC. Then, the effects of PHGDH knockdown on ESCC were evaluated in vitro and in vivo by cell proliferation, clone formation, cell cycle, apoptosis, tube formation assays and ESCC cells derived xenograft model. In addition, western blotting and immunohistochemistry were used to detect the expression of Wnt/β-catenin pathway which was associated with PHGDH. ResultsBioinformatics analysis found that PHGDH was highly expressed in ESCC, and meaningfully, patients with high PHGDH expression had a poor prognosis. Moreover, the overexpression of PHGDH was verified in ESCC. Afterwards, PHGDH knockdown inhibited the cell proliferation, induced cell cycle arrest and apoptosis in ESCC cells, and inhibited the angiogenesis of HUVECs induced by ESCC conditioned medium, as well as inhibited the growth of xenograft tumor. Mechanistically, PHGDH knockdown inhibited Wnt/β-catenin signaling pathway in ESCC. ConclusionHigh expression of PHGDH predicts a poor prognosis for ESCC. PHGDH knockdown inhibits ESCC progression by suppressing Wnt/β-catenin signaling pathway, indicating that PHGDH might be a potential target for ESCC therapy.