Mechanosensitive hormone signaling promotes mammary progenitor expansion and breast cancer risk.

ABSTRACT: Tissue stem-progenitor cell frequency has been implicated in tumor risk and progression, but tissue-specific factors linking these associations remain ill-defined. We observed that stiff breast tissue from women with high mammographic density, who exhibit increased lifetime risk for breast cancer, associates with abundant stem-progenitor epithelial cells. Using genetically engineered mouse models of elevated integrin mechanosignaling and collagen density, syngeneic manipulations, and spheroid models, we determined that a stiff matrix and high mechanosignaling increase mammary epithelial stem-progenitor cell frequency and enhance tumor initiation in vivo. Augmented tissue mechanics expand stemness by potentiating extracellular signal-related kinase (ERK) activity to foster progesterone rece

SUBMITTER: Northey JJ 

PROVIDER: S-EPMC11050720 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature