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Int. J. Mol. Sci. 2014, 15(11), 20706-20722; doi:10.3390/ijms151120706

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

1
Department of Oncology, Xijing Hospital, the Fourth Military Medical University, Xi'an 710032, China
2
Department of Oncology, General Hospital of Shenyang Military Area Command, Shenyang 110840, China
3
Key Laboratory of Aerospace Medicine, Ministry of Education, the Fourth Military Medical University, Xi'an 710032, China
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 14 August 2014 / Revised: 9 October 2014 / Accepted: 22 October 2014 / Published: 12 November 2014
(This article belongs to the Collection Proteins and Protein-Ligand Interactions)
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Abstract

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. View Full-Text
Keywords: caveolin-1; large conductance Ca2+-activated potassium (BKCa) channel; breast cancer; proliferation; invasion caveolin-1; large conductance Ca2+-activated potassium (BKCa) channel; breast cancer; proliferation; invasion
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Du, C.; Chen, L.; Zhang, H.; Wang, Z.; Liu, W.; Xie, X.; Xie, M. Caveolin-1 Limits the Contribution of BKCa Channel to MCF-7 Breast Cancer Cell Proliferation and Invasion. Int. J. Mol. Sci. 2014, 15, 20706-20722.

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