Caveolin-1 limits the contribution of BKCa channel to MCF-7 breast cancer cell proliferation and invasion.
Caveolin-1 limits the contribution of BKCa channel to MCF-7 breast cancer cell proliferation and invasion.
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DOI：
10.3390/ijms151120706
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发表时间：
2014-11-12
影响因子：
5.6
通讯作者：
Xie M
中科院分区：
文献类型：
--
作者：
Du C;Chen L;Zhang H;Wang Z;Liu W;Xie X;Xie M
越来越多的证据表明，小窝蛋白-1和大电导钙激活钾（BKCa）通道涉及的致癌过程，包括细胞增殖和侵袭。这两种蛋白质已被证明在血管内皮细胞和平滑肌细胞中相互作用并调节血管收缩性。在这项研究中，我们研究了MCF-7乳腺癌细胞中小窝蛋白-1和BKCa之间可能的相互作用。我们发现，小窝蛋白-1和BKCa的共定位，并可以在人乳腺癌MCF-7细胞中的免疫共沉淀。siRNA介导的caveolin-1基因敲低可激活BKCa通道，增加BKCa通道的表达，促进乳腺癌细胞的增殖和侵袭。这些作用在BKCa-siRNA存在下减弱。相反，上调caveolin-1抑制BKCa通道的功能和表面表达，对乳腺癌细胞的增殖和侵袭产生负面影响。类似地，这些相反的作用被BKCa上调所消除。总的来说，我们的研究结果表明，BKCa是小窝蛋白-1抑制乳腺癌细胞增殖和侵袭的关键靶点。Caveolin-1与BKCa在乳腺癌细胞膜微区的功能复合物可能成为乳腺癌治疗的潜在靶点。
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.
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影响因子：
4.2
作者：
Gumulec, Jaromir;Sochor, Jiri;Masarik, Michal
通讯作者：
Masarik, Michal
影响因子：
3.8
作者：
Khaitan D;Sankpal UT;Weksler B;Meister EA;Romero IA;Couraud PO;Ningaraj NS
通讯作者：
Ningaraj NS
唑来膦酸诱导 MDA-MB-231 乳腺癌细胞凋亡中 BKCa 通道的激活
影响因子：
3.7
作者：
Ma YG;Liu WC;Dong S;Du C;Wang XJ;Li JS;Xie XP;Wu L;Ma DC;Yu ZB;Xie MJ
通讯作者：
Xie MJ
影响因子：
3.7
作者：
Oeggerli M;Tian Y;Ruiz C;Wijker B;Sauter G;Obermann E;Güth U;Zlobec I;Sausbier M;Kunzelmann K;Bubendorf L
通讯作者：
Bubendorf L
影响因子：
11.2
作者：
Chiu WT;Lee HT;Huang FJ;Aldape KD;Yao J;Steeg PS;Chou CY;Lu Z;Xie K;Huang S
通讯作者：
Huang S