Activation of hERG3 channel stimulates autophagy and promotes cellular senescence in melanoma Journal Article

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Authors: Perez-Neut, M.; Haar, L; Rao, V; Santha, S.; Lansu, K.; Rana, B.; Jones, W. K.; Gentile, S
Article Title: Activation of hERG3 channel stimulates autophagy and promotes cellular senescence in melanoma
Abstract: 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.
Journal Title: Oncotarget
ISSN: 1949-2553; 1949-2553
Publisher: Unknown  
Date Published: 2016
Language: ENG
DOI/URL:

10.18632/oncotarget.7831
Notes: LR: 20160305; JID: 101532965; OTO: NOTNLM; 2016/01/12 [received]; 2016/02/15 [accepted]; aheadofprint