GPR87 Promotes Angiogenesis in Esophageal Squamous Cell Carcinoma via VEGFA Regulation

The role and underlying mechanisms of G protein-coupled receptor 87 (GPR87) in esophageal squamous cell carcinoma (ESCC) remain unclear, despite its established oncogenic functions in Other malignancies. This study examined the expression of GPR87 and its association with survival rate in ESCC using online databases. The expression of GPR87 in ESCC tissues was identified using immunohistochemistry, and a correlation analysis was carried out using ki-67 data. ESCC cells were transfected with GPR87 knockdown or overexpression plasmids, followed by functional assays such as, CCK-8 for cell viability, colony formation for proliferation, wound healing for migration, Transwell for invasion, and tube formation for angiogenesis. Western blot analysis was used to assess STAT3 phosphorylation and VEGFA expression. Additionally, a xenograft tumor model was established to investigate the effect of GPR87 on tumor growth in vivo. The findings demonstrated that GPR87 was highly expressed in ESCC tissues and its overexpression was associated with a poor patient survival. Transfection with a GPR87 overexpression plasmid increases the cell viability, invasion, proliferation, and angiogenesis of ESCC cells, while transfection with sh-GPR87 reversed these effects. Additionally, GPR87 controlled VEGFA expression levels by promoting STAT3 phosphorylation. Rescue trials further verified that GPR87 promotes the growth of ESCC by modulating STAT3. Moreover, in vivo studies validated that GPR87 knockdown suppressed tumor growth. In conclusion, the findings highlight GPR87 as a key regulator of VEGFA expression via STAT3 activation, contributing to ESCC malignancy. Targeting GPR87 may provide a potential therapeutic strategy for ESCC.

G protein‐coupled receptor 87; Migration and angiogenesis; STAT3/VEGFA pathway; esophageal squamous cell carcinoma; tumor progression.