{"title":"EpCAM-dependent membrane mechanics regulate nuclear deformation and promote gastric cancer metastasis.","authors":"Guoqiao Chen, Mengting Jiang, Jing Yang, Xiaolong Liu, Jiaxi Cheng, Qiming Xia, Yixuan Li, Wei Liu, Xiaoxiao Fan, Hui Lin","doi":"10.1016/j.celrep.2026.118126","DOIUrl":null,"url":null,"abstract":"<p><p>Diffuse gastric cancer is highly metastatic and lacks effective therapeutic targets. Using membrane proteomics, gastric cancer cell models, biophysical measurements, and in vivo metastasis assays, we identify EpCAM as a regulator of membrane-cytoskeletal mechanics. EpCAM overexpression was associated with reduced apparent plasma membrane tension, ERM-actin remodeling, increased traction forces, and nuclear deformation. Functional perturbation of ezrin and lamin A/C supported the involvement of membrane-cytoskeleton-nucleus mechanical coupling in confined migration. EpCAM knockout or monoclonal antibody blockade reduced tumor invasion and lymph node dissemination in vivo. These findings establish a mechanobiological framework linking EpCAM-dependent membrane mechanics to metastatic behavior and highlight EpCAM-associated mechanical regulation as a potential therapeutic vulnerability in diffuse gastric cancer.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118126"},"PeriodicalIF":7.7000,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell reports","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.celrep.2026.118126","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Diffuse gastric cancer is highly metastatic and lacks effective therapeutic targets. Using membrane proteomics, gastric cancer cell models, biophysical measurements, and in vivo metastasis assays, we identify EpCAM as a regulator of membrane-cytoskeletal mechanics. EpCAM overexpression was associated with reduced apparent plasma membrane tension, ERM-actin remodeling, increased traction forces, and nuclear deformation. Functional perturbation of ezrin and lamin A/C supported the involvement of membrane-cytoskeleton-nucleus mechanical coupling in confined migration. EpCAM knockout or monoclonal antibody blockade reduced tumor invasion and lymph node dissemination in vivo. These findings establish a mechanobiological framework linking EpCAM-dependent membrane mechanics to metastatic behavior and highlight EpCAM-associated mechanical regulation as a potential therapeutic vulnerability in diffuse gastric cancer.
期刊介绍：
Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted.
The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership.
The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
