Cancer-associated fibroblasts promote directional cancer cell migration by aligning fibronectin

Cancer-associated fibroblasts (CAFs) are major components of the carcinoma microenvironment that promote tumor progression. However, the mechanisms by which CAFs regulate cancer cell migration are poorly understood. In this study, we show that fibronectin (Fn) assembled by CAFs mediates CAF-cancer cell association and directional migration. Compared with normal fibroblasts, CAFs produce an Fn-rich extracellular matrix with anisotropic fiber orientation, which guides the cancer cells to migrate directionally. CAFs align the Fn matrix by increasing nonmuscle myosin II- and platelet-derived growth factor receptor α-mediated contractility and traction forces, which are transduced to Fn through α5β1 integrin. We…

• VU
  Vanderbilt University
• NI
  National Institutes of Health

  Awards: GISPORE 5P50 CA095103-13, R01CA206458, 5P30 DK058404-13, CA155572, R01CA163592, GM117916, 5U01 CA151924