Matrix stiffness drives stromal autophagy and promotes formation of a protumorigenic niche

Significance Increased tissue stiffness is a hallmark of several diseases such as organ fibrosis or cancer, and tissue fibroblasts play central roles in these pathologies. In tumors, stromal cells support the growth of cancer cells by supplying signaling molecules and nutrients, the latter also being provided by stromal autophagy. The mechanisms inducing these processes are, however, not well understood. Here, we demonstrate that an increased physical rigidity of a fibroblast’s environment is sufficient to evoke stromal autophagy. Mechanistically, matrix stiffness is transmitted via Integrin αV receptors and focal adhesion kinase, resulting in stabilization of AMPK at focal adhesion structures. Stiffness-mediated stromal autophagy supports the growth of neighboring tumor cells in vitro and in vivo, opening possibilities for anti-cancer therapies.