https://ror.org/02jx3x895 Department of Medical Physics and Biomedical Engineering, Malet Place Engineering Building, University College London, London, UK
Institute for Early Detection, CRUK Cambridge Centre, Cambridge, UK.
Life Sci Alliance. 2023 Sep 25;6(12). doi: 10.26508/lsa.202302124. Print 2023 Dec.
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 family genes are mutated in ∼30% of patients, and play therapeutically targetable roles in GOA cancer growth. and mediate the WNT pathway and MYC to increase proliferation through resultant effects on cadherin junctions. This also highlights novel roles of 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.
电压门控钾通道在控制肠道膜电位和离子动态平衡方面发挥着重要作用，并且与胃肠道（GI）癌症有关。通过对 897 名胃食管腺癌（GOA）患者进行大规模分析，并结合体外模型，我们发现家族基因在约 30%的患者中发生突变，并在 GOA 癌症生长中发挥可治疗靶向作用。和 介导 WNT 途径和 MYC 通过对钙黏着蛋白连接的影响来增加增殖。这也突出了 在非兴奋性组织中的新作用。我们还发现，KCNQ3 的活性使癌细胞对现有的钾通道抑制剂敏感，并且抑制 KCNQ 活性会降低 GOA 癌细胞的增殖。这些发现揭示了钾通道在人类癌症进展中的新的和可利用的作用，并强调通过 KCNQ 抑制剂可能存在针对 GOA 的补充治疗方法。
