Mechanical compression drives cancer cells toward invasive phenotype

TLDR

Tumor growth in confined spaces generates compressive stress, yet its effect on cancer cell behavior is poorly understood. The study seeks to target this stress‑induced mechanism to prevent cancer cell migration and invasion. Compressive stress promotes mammary carcinoma migration by inducing leader cells with enhanced filopodia, fibronectin deposition, and stronger adhesion, resulting in coordinated, actomyosin‑independent movement.

Abstract

Uncontrolled growth in a confined space generates mechanical compressive stress within tumors, but little is known about how such stress affects tumor cell behavior. Here we show that compressive stress stimulates migration of mammary carcinoma cells. The enhanced migration is accomplished by a subset of “leader cells” that extend filopodia at the leading edge of the cell sheet. Formation of these leader cells is dependent on cell microorganization and is enhanced by compressive stress. Accompanied by fibronectin deposition and stronger cell–matrix adhesion, the transition to leader-cell phenotype results in stabilization of persistent actomyosin-independent cell extensions and coordinated migration. Our results suggest that compressive stress accumulated during tumor growth can enable coordinated migration of cancer cells by stimulating formation of leader cells and enhancing cell–substrate adhesion. This novel mechanism represents a potential target for the prevention of cancer cell migration and invasion.