一二三四区视频,亚洲少妇熟女色,日本久热无码视频网,欧美国产日韩大尺度,亚洲a视频,久久少妇一区二区,日韩999无码视频,刺激久久久久久久,啊啊啊啊不要啊在线

ChemicalBook >> journal list >> Oncogene >>article
Oncogene

Oncogene

IF: 7.3
Download PDF

Cancer-associated loss-of-function mutations in KCNQ1 enhance Wnt/β-catenin signalling disrupting epithelial homeostasis

Published:23 May 2025 DOI: 10.1038/s41388-025-03447-4 PMID: 40410368
Camille Berenguier, Xingyu Chen, Benoit Allegrini, Hélène Guizouarn, Franck Borgese, Catherine Etchebest, Olivier Soriani, Raphael Rapetti-Mauss

Abstract

Ion channels are emerging as regulators of intracellular signalling pathway, yet the molecular mechanisms underlying this role remain poorly understood. KCNQ1, a potassium channel with tumour suppressor functions, restricts Wnt/β-catenin signalling, a pathway whose dysregulation, often driven by protein-altering mutations, is a hallmark of several epithelial cancers. Here, we identify loss-of-function (LOF) mutations in KCNQ1 across multiple epithelial cancers and elucidate their impact on Wnt/β-catenin signalling. Our findings reveal that cancer-associated KCNQ1-LOF mutations regulate the β-catenin pathway through a dual mechanism. First, they drive β-catenin transcriptional activity through triggering MET receptor, bypassing Frizzled/LRP6 receptor complex activation. Second, these mutations suppress the expression of key negative regulators of Wnt signalling, such as DKK-1, Wif-1 and NKD-1, leading to amplified pathway activation in response to Wnt ligand stimulation. This dysregulation disrupts epithelial homeostasis, as demonstrated by impaired crypt organization and increased proliferation in mouse colon-derived organoids. Together, these findings uncover an original mechanism linking KCNQ1 dysfunction to aberrant Wnt/β-catenin signalling, highlighting the role of ion channels in regulating epithelial signalling networks and tissue homeostasis.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Y27632 (hydrochloride) 129830-38-2 C14H23Cl2N3O 226 suppliers $23.00-$5472.00
Y27632 (hydrochloride) 129830-38-2 C14H23Cl2N3O 226 suppliers $23.00-$5472.00
Y27632 (hydrochloride) 129830-38-2 C14H23Cl2N3O 226 suppliers $23.00-$5472.00
Y27632 (hydrochloride) 129830-38-2 C14H23Cl2N3O 226 suppliers $23.00-$5472.00

Similar articles

IF:4.5

Antimicrobial agent chloroxylenol targets β?catenin?mediated Wnt signaling and exerts anticancer activity in colorectal cancer.

International journal of oncology Qi Sun, Boxin Liu,etc Published: 1 November 2023
IF:5.6

D-tryptophan triggered epithelial-mesenchymal transition by activating TGF-β signaling pathway

Food Science and Human Wellness Chong Wang, Fangting Wang,etc Published: 1 September 2022
浦城县| 容城县| 西藏| 西藏| 鹤峰县| 长泰县| 怀仁县| 宾阳县| 麦盖提县| 日照市| 静海县| 中牟县| 息烽县| 大名县| 庆安县| 开化县| 寿宁县| 全南县| 临颍县| 胶州市| 台州市| 嘉祥县| 肇州县| 天津市| 牡丹江市| 剑阁县| 治县。| 井冈山市| 涟源市| 通渭县| 岳阳县| 大同市| 民和| 徐汇区| 云龙县| 凤阳县| 绥德县| 仙桃市| 贵州省| 乌兰察布市| 安龙县|