Cancer associated fibroblasts: is the force the path to the dark side?

The most abundant cell type in the tumor microenvironment are cancer-associated fibroblasts (CAFs). CAFs play an important role in tumor growth and progression. Besides direct communication with cancer cells via secreted molecules or cell–cell adhesions, CAFs also indirectly affect cancer cell behavior by remodeling the extracellular matrix (ECM). Here, we summarize recent findings on the distinct mechanisms that CAFs use to modify ECM, specifically, their proteolytic versus force-dependent activity. We then review the consequences of CAF force transmission on the physico-chemical properties of the matrix, focusing on the deposition of new matrix components, and the alteration of the organization and stiffness of the ECM. CAFs promote tumor invasion by creating the roads cancer cells use to escape the tumor mass. However, there is also evidence that CAFs can prevent invasion, possibly by forming a physical barrier around the tumor edge. We discuss the controversial role of CAFs in tumor progression.