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

Journal Article (Journal Article)

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 further show that prostate cancer cells use αv integrin to migrate efficiently and directionally on CAF-derived matrices. We demonstrate that aligned Fn is a prominent feature of invasion sites in human prostatic and pancreatic carcinoma samples. Collectively, we present a new mechanism by which CAFs organize the Fn matrix and promote directional cancer cell migration.

Full Text

Duke Authors

Cited Authors

  • Erdogan, B; Ao, M; White, LM; Means, AL; Brewer, BM; Yang, L; Washington, MK; Shi, C; Franco, OE; Weaver, AM; Hayward, SW; Li, D; Webb, DJ

Published Date

  • November 6, 2017

Published In

Volume / Issue

  • 216 / 11

Start / End Page

  • 3799 - 3816

PubMed ID

  • 29021221

Pubmed Central ID

  • PMC5674895

Electronic International Standard Serial Number (EISSN)

  • 1540-8140

Digital Object Identifier (DOI)

  • 10.1083/jcb.201704053


  • eng

Conference Location

  • United States