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24 April 2020 : Laboratory Research  

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

Hong Yu1ADEG*, Xiaoqin Jiang1BCF, Lin Jiang2BCD, Huiling Zhou1BC, Jingjing Bao1BF, Xiaowei Zhu1BF, Fuxing Liu1BF, Junxing Huang3ACDEG

DOI: 10.12659/MSM.920665

Med Sci Monit 2020; 26:e920665

Abstract

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 AND 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.

Keywords: Cadherins, Esophageal Neoplasms, Neoplasm Metastasis, RNA, Small Untranslated, 3' Untranslated Regions, Apoptosis, Cell Movement, Cell Proliferation, Epithelial-mesenchymal transition, esophageal squamous cell carcinoma, Mice, Inbred BALB C, MicroRNAs, Neoplasm Invasiveness, Neovascularization, Pathologic, Protocadherins, Signal Transduction, Vascular Endothelial Growth Factor A, Xenograft Model Antitumor Assays

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750