Figure 2.

Players, mechanisms, and implications of ECM remodeling in cancer. Cancer cells, cancer-associated fibroblasts (CAFs), and extracellular vesicles (EVs) are the major players involved in cancer ECM remodeling. All three players have large roles in ECM degradation through the release of matrix metalloproteinases (MMPs), leading to altered ECM topography and the generation of tracks in the ECM. Additionally, cancer cells, CAFs, and EVs have all been implicated in matrix deposition of various proteins, leading to matrix stiffening. Cancer cells, CAFs, and EVs are involved in matrix crosslinking to stiffen the matrix through tissue transglutaminase (TG2) and lysyl oxidase (LOX). Both cancer cells and CAFs are highly involved in physical remodeling of the ECM, both through actomyosin contractility and cell–matrix adhesion complexes (CMACs).