CAV3.1 knockdown suppresses cell proliferation, migration and invasion of prostate cancer cells by inhibiting AKT.

Abstract

BackgroundAberrant expression of CAV3.1, one of T-type Ca2+ channels, is reported to exert important functions in pathological processes, including carcinogenesis. However, its expression pattern and function in prostate cancer (PCa) remains unclear.Materials and methodsThe expression pattern of CAV3.1 was analyzed in multiple ways, including online analysis in Oncomine database, experimental analyses in cell lines, and collected clinical specimens using immunohistochemistry, quantitative reverse transcription polymerase chain reaction, and Western blot. Then, CAV3.1 was downregulated in PCa cells to explore its functions.ResultsUpregulated CAV3.1 in PCa tissues and cells was confirmed by analyzing mRNA expression datasets from Oncomine and quantitative reverse transcription polymerase chain reaction detection, respectively. Accordingly, significantly higher CAV3.1 protein level in PCa tissues specimens than that in benign prostatic hyperplasia tissues was indicated by immunohistochemical staining. In addition, CAV3.1 upregulation was positively associated with metastasis. Depletion of CAV3.1 impaired the proliferation, migration, and invasion ability of PCa cells demonstrating by cell functional experiments, such as CCK-8, cell cycle distribution, plate clone formation, scratch wound healing, and transwell invasion assays. Mechanistically, due to constrained Akt activity, CAV3.1 knockdown resulted in decreased level of CCND1, N-cadherin, and Vimentin, and increased level of E-cadherin whose expressions could be reversed by ectopic Akt expression. Similarly, ectopic Akt expression also rescued the inhibitory effects of CAV3.1 knockdown on cell functions like proliferation and migration in PCa cells.ConclusionUpregulated CAV3.1 is positively associated with the development of PCa. CAV3.1 knockdown can inhibit PCa cell proliferation, migration, and invasion by suppressing AKT activity.