KCNQ potassium channels modulate Wnt activity in gastro-oesophageal adenocarcinomas.
- Resource Type
- Academic Journal
- Authors
- Shorthouse D; https://ror.org/02jx3x895 Department of Medical Physics and Biomedical Engineering, Malet Place Engineering Building, University College London, London, UK d.shorthouse@ucl.ac.uk.; Zhuang L; Institute for Early Detection, CRUK Cambridge Centre, Cambridge, UK.; Rahrmann EP; Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge, UK.; Kosmidou C; Institute for Early Detection, CRUK Cambridge Centre, Cambridge, UK.; Wickham Rahrmann K; Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge, UK.; Hall M; Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge, UK.; Greenwood B; https://ror.org/02jx3x895 Department of Medical Physics and Biomedical Engineering, Malet Place Engineering Building, University College London, London, UK.; Devonshire G; Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge, UK.; Gilbertson RJ; Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge, UK.; Fitzgerald RC; Institute for Early Detection, CRUK Cambridge Centre, Cambridge, UK.; Hall BA; https://ror.org/02jx3x895 Department of Medical Physics and Biomedical Engineering, Malet Place Engineering Building, University College London, London, UK b.hall@ucl.ac.uk.
- Source
- Publisher: Life Science Alliance, LLC Country of Publication: United States NLM ID: 101728869 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 2575-1077 (Electronic) Linking ISSN: 25751077 NLM ISO Abbreviation: Life Sci Alliance Subsets: MEDLINE
- Subject
- Language
- English
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.
(© 2023 Shorthouse et al.)