Work

EpCAM-dependent membrane mechanics regulate nuclear deformation and promote gastric cancer metastasis

Year: 2026

Type: article

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.

Source: Cell Reports

DOI: 10.1016/j.celrep.2026.118126