MUC15 Ectodomain Architecture Regulates Integrin Clustering to Control Cancer Metastasis.

ABSTRACT: Cancer metastasis is governed by physical cues at the cell-matrix interface, with matrix stiffness, ligand density, and topography established as key determinants. Here, a fourth critical factor in cancer metastasis, the architecture of the cell-surface glycocalyx is identified. Using MUC15 as a representative small glycoprotein, mathematical modeling and domain truncation experiments are combined to show that glycoprotein size distribution governs integrin adhesion states and metastatic outcomes. MUC15 localizes to focal adhesions and interact with integrins, while larger glycoproteins such as MUC1 are sterically excluded. These physical effects, rather than intracellular signaling, dictate adhesion state transitions: removing MUC15's ectodomain eliminated its anti-metastatic effects, whe

SUBMITTER: Zhang S 

PROVIDER: S-EPMC12752613 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature