CAV3.1 knockdown suppresses cell proliferation, migration and invasion of prostate cancer cells by inhibiting AKT
Authors Hu SB, Li L, Huang W, Liu J, Lan G, Yu S, Peng L, Xie X, Yang L, Nian Y, Wang Y
Received 3 May 2018
Accepted for publication 13 June 2018
Published 15 October 2018 Volume 2018:10 Pages 4603—4614
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Cristina Weinberg
Peer reviewer comments 3
Editor who approved publication: Dr Antonella D'Anneo
Shanbiao Hu,1 Ling Li,2 Wei Huang,3 Jie Liu,4 Gongbin Lan,1 Shaojie Yu,1 Longkai Peng,1 Xubiao Xie,1 Luoyan Yang,2 Yeqi Nian,2 Yinhuai Wang2
1Department of Urological Organ Transplantation, The Second Xiangya Hospital of Central South University, Changsha, China; 2Department of Urology, The Second Xiangya Hospital of Central South University, Changsha, China; 3Research Center of Carcinogenesis and Targeted Therapy, Xiangya Hospital, Central South University, Changsha, China; 4Department of Pathology, Changsha Central Hospital, Changsha, China
Background: Aberrant 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 methods: The 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.
Results: Upregulated 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.
Conclusion: Upregulated 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.
Keywords: CAV3.1, PCa, AKT signaling, proliferation, invasion
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