Molecular Control of Tissue Fluidification Links Epithelial Mechanics to Anti-Tumor Immunity

Epithelial tissues can transition from jammed, solid-like states to fluid-like regimes, enabling coordinated migration in cancer. We define a mechanochemical program linking epithelial mechanics to anti-tumor immunity. EGF induces de novo transcription of connexins, promoting gap junction–mediated intercellular fluid exchange, generating density fluctuations and cell shape variability that trigger collective flocking. In parallel, RAB5A-dependent endocytosis drives tissue fluidification, leading to nuclear deformation and mitochondrial DNA release, activating cGAS/STING and interferon responses. In ductal carcinoma in situ, this enhances invasion and tumor immunogenicity.

Chair: Alessandra Cambi