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<p>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 evaluated the hypothesis that pharmacologic activation of the Kv11.1 channel in lung cancer may impair tumor growth. We discovered that Kv11.1 activation inhibits lung cancer growth by inducing a senescent phenotype. Moreover, we found that pharmaceutical Kv11.1 opening produced a 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 anticancer pharmacological strategy against lung adenocarcinomas.</p><p></p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月20日

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  • Najmeh Eskandari,
  • Davide Delisi,
  • Richard O’Neil,
  • Maurizio Bocchetta,
  • Saverio Gentile

摘要

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 evaluated the hypothesis that pharmacologic activation of the Kv11.1 channel in lung cancer may impair tumor growth. We discovered that Kv11.1 activation inhibits lung cancer growth by inducing a senescent phenotype. Moreover, we found that pharmaceutical Kv11.1 opening produced a 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 anticancer pharmacological strategy against lung adenocarcinomas.