Activation of hERG3 channel stimulates autophagy and promotes cellular senescence in melanoma.
Activation of hERG3 channel stimulates autophagy and promotes cellular senescence in melanoma.
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DOI：
10.18632/oncotarget.7831
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发表时间：
2016-04-19
期刊：
影响因子：
--
通讯作者：
Gentile S
中科院分区：
文献类型：
--
作者：
Perez-Neut M;Haar L;Rao V;Santha S;Lansu K;Rana B;Jones WK;Gentile S
Ion channels play a major factor in maintaining cellular homeostasis but very little is known about the role of these proteins in cancer biology. In this work we have discovered that, the Kv11.3 (hERG3) a plasma-membrane potassium channel plays a critical role in the regulation of autophagy in a cancer cell model. We have found that pharmacologic stimulation of the Kv11.3 channel with a small molecule activator, NS1643 induced autophagy via activation of an AMPK-dependent signaling pathway in melanoma cell line. In addition, we have found that NS1643 produced a strong inhibition of cell proliferation by activating a cellular senescence program. Furthermore, inhibition of autophagy via siRNA targeting AMPK or treatment with hydroxychloroquine an autophagy inhibitor activates apoptosis in NS1643-treated cells. Thus, we propose that, Kv11.3 is a novel mediator of autophagy, autophagy can be a survival mechanism contributing to cellular senescence, and that use of a combinatorial pharmacologic approach of Kv11.3 activator with inhibitors of autophagy represents a novel therapeutic approach against melanoma.
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影响因子：
64.5
作者：
Burd CE;Sorrentino JA;Clark KS;Darr DB;Krishnamurthy J;Deal AM;Bardeesy N;Castrillon DH;Beach DH;Sharpless NE
通讯作者：
Sharpless NE
影响因子：
30.8
作者：
Krauthammer, Michael;Kong, Yong;Ha, Byung Hak;Evans, Perry;Bacchiocchi, Antonella;McCusker, James P.;Cheng, Elaine;Davis, Matthew J.;Goh, Gerald;Choi, Murim;Ariyan, Stephan;Narayan, Deepak;Dutton-Regester, Ken;Capatana, Ana;Holman, Edna C.;Bosenberg, Marcus;Sznol, Mario;Kluger, Harriet M.;Brash, Douglas E.;Stern, David F.;Materin, Miguel A.;Lo, Roger S.;Mane, Shrikant;Ma, Shuangge;Kidd, Kenneth K.;Hayward, Nicholas K.;Lifton, Richard P.;Schlessinger, Joseph;Boggon, Titus J.;Halaban, Ruth
通讯作者：
Halaban, Ruth
影响因子：
4.8
作者：
Liu, Chao;Liang, Bin;Zou, Ming-Hui
通讯作者：
Zou, Ming-Hui
影响因子：
21.3
作者：
通讯作者：
--
DOI：
10.18632/aging.100281
发表时间：
2011-02
期刊：
Aging
影响因子：
--
作者：
Blagosklonny MV
通讯作者：
Blagosklonny MV