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Updated: Jul 15, 2025

The Soft Agar Colony Formation Assay
Published on: October 27, 2014
KCNQ potassium channels modulate Wnt activity in gastro-oesophageal adenocarcinomas
David Shorthouse1, Lizhe Zhuang2, Eric P Rahrmann3
1Department of Medical Physics and Biomedical Engineering, Malet Place Engineering Building, University College London, London, UK d.shorthouse@ucl.ac.uk.
Abstract:
Voltage-sensitive potassium channels play an important role in controlling membrane potential and ionic homeostasis in the gut and have been implicated in gastrointestinal (GI) cancers. Through large-scale analysis of 897 patients with gastro-oesophageal adenocarcinomas (GOAs) coupled with in vitro models, we find KCNQ family genes are mutated in ∼30% of patients, and play therapeutically targetable roles in GOA cancer growth. KCNQ1 and KCNQ3 mediate the WNT pathway and MYC to increase proliferation through resultant effects on cadherin junctions. This also highlights novel roles of KCNQ3 in non-excitable tissues. We also discover that activity of KCNQ3 sensitises cancer cells to existing potassium channel inhibitors and that inhibition of KCNQ activity reduces proliferation of GOA cancer cells. These findings reveal a novel and exploitable role of potassium channels in the advancement of human cancer, and highlight that supplemental treatments for GOAs may exist through KCNQ inhibitors.
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