Protocadherin 8 (PCDH8) Inhibits Proliferation, Migration, Invasion, and Angiogenesis in Esophageal Squamous Cell Carcinoma

BACKGROUND: Protocadherin 8 (PCDH8) functions as a tumor-suppressor gene in many types of cancer. This study aimed to investigate the role of PCDH8 in esophageal squamous cell carcinoma (ESCC). MATERIAL/METHODS: Cell proliferation, apoptosis, transwell assay, tube formation assays, and tumor xenograft experiment were performed to explore the role of PCDH8 in the progression of ESCC. RESULTS: PCDH8 was found to be downregulated in ESCC cells. Ectopic expression of PCDH8 blocked proliferation, invasion, and migration and induced apoptosis in ESCC cells. Furthermore, vascular endothelial growth factor A (VEGFA) secretion and the AKT signaling pathway were also inhibited when PCDH8 was upregulated. PCDH8 overexpression suppressed epithelial-mesenchymal transition (EMT) and pro-angiogenic activity of ESCC cells. In a mouse model of ESCC xenograft tumors, PCDH8 overexpression remarkably restrained tumor cell growth, with the tumor inhibition rate of 75.2%. PCDH8 was the target of miR-200c and had a negative correlation with miR-200c. CONCLUSIONS: PCDH8 exerts a tumor-suppressive effect against ESCC cells. However, further studies are required to elucidate the exact molecular mechanism underlying the antitumor activity of PCDH8 in ESCC.