Caveolin-1 Limits the Contribution of BKCa Channel to MCF-7 Breast Cancer Cell Proliferation and Invasion

International Journal of Molecular Sciences

Cheng Du³  Li Chen¹  Haijun Zhang¹  Zhongchao Wang¹  Wenchao Liu³  Xiaodong Xie²  Manjiang Xie¹ 

[1] Key Laboratory of Aerospace Medicine, Ministry of Education, the Fourth Military Medical University, Xi’an 710032, China; E-Mails:;Department of Oncology, General Hospital of Shenyang Military Area Command, Shenyang 110840, China;Department of Oncology, Xijing Hospital, the Fourth Military Medical University, Xi’an 710032, China; E-Mail:

关键词: caveolin-1;    large conductance Ca²⁺-activated potassium (BKCa) channel;    breast cancer;    proliferation;    invasion;   

DOI  :  10.3390/ijms151120706

来源: mdpi

【 摘 要 】

Increasing evidence suggests that caveolin-1 and large conductance Ca²⁺-activated potassium (BKCa) channels are implicated in the carcinogenesis processes, including cell proliferation and invasion. These two proteins have been proven to interact with each other in vascular endothelial and smooth muscle cells and modulate vascular contractility. In this study, we investigated the probable interaction between caveolin-1 and BKCa in MCF-7 breast cancer cells. We identified that caveolin-1 and BKCa were co-localized and could be reciprocally co-immunoprecipitated in human breast cancer MCF-7 cells. siRNA mediated caveolin-1 knockdown resulted in activation and increased surface expression of BKCa channel, and subsequently promoted the proliferation and invasiveness of breast cancer cells. These effects were attenuated in the presence of BKCa-siRNA. Conversely, up-regulated caveolin-1 suppressed function and surface expression of BKCa channel and exerted negative effects on breast cancer cell proliferation and invasion. Similarly, these opposing effects were abrogated by BKCa up-regulation. Collectively, our findings suggest that BKCa is a critical target for suppression by caveolin-1 in suppressing proliferation and invasion of breast cancer cells. The functional complex of caveolin-1 and BKCa in the membrane microdomain may be served as a potential therapeutic target in breast cancer.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.