Matrix mechanics regulates epithelial defence against cancer by tuning dynamic localization of filamin.

ABSTRACT: In epithelia, normal cells recognize and extrude out newly emerged transformed cells by competition. This process is the most fundamental epithelial defence against cancer, whose occasional failure promotes oncogenesis. However, little is known about what factors determine the success or failure of this defence. Here we report that mechanical stiffening of extracellular matrix attenuates the epithelial defence against HRas^V12-transformed cells. Using photoconversion labelling, protein tracking, and loss-of-function mutations, we attribute this attenuation to stiffening-induced perinuclear sequestration of a cytoskeletal protein, filamin. On soft matrix mimicking healthy epithelium, filamin exists as a dynamically single population, which moves to the normal cell-transformed cell

SUBMITTER: Pothapragada SP 

PROVIDER: S-EPMC8752856 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature