Activation of Kv11.1 potassium channel suppresses lung cancer growth by promoting c-Myc degradation.

The Kv11.1 potassium channels and the transcription factor c-Myc both play fundamental roles in controlling cellular homeostasis. Cancers take advantage of dysregulated c-Myc and Kv11.1, however, little is known about the possible link between these proteins. In this work we found that an inverse relationship between c-MYC and Kv11.1 exists in some lung adenocarcinoma. Importantly, patients expressing an elevated level of the Kv11.1 channel present a better overall survival when compared with patients with low expression. Therefore, we evaluate the hypothesis that pharmacologic activation of the Kv11.1 channel in lung cancer affects tumor growth. Our experimental tests provide definitive evidence a Kv11.1 agonist inhibits lung cancer growth by activating a senescent phenotype. Remarkably, we found that Kv11.1 activation produced rapid proteasomal degradation of c-Myc and that this could be antagonized by the OTUD6B deubiquitinase. We concluded that use of Kv11.1 agonists should be considered as potent anticancer pharmacological strategy against lung adenocarcinomas.