Referenced in: none

Automatically associated channels: Kv11.1 , Kv11.3

Title: Activation of hERG3 channel stimulates autophagy and promotes cellular senescence in melanoma.

Authors: Mathew Perez-Neut, Lauren Haar, Vidhya Rao, Sreevidya Santha, Katherine Lansu, Basabi Rana, Walter K Jones, Saverio Gentile

Journal, date & volume: Oncotarget, 2016 Mar 1 , ,

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/26942884

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.