These conclusions are based upon the following critical findings: (1) human-derived cancer associated fibroblasts potentiate in vitro invasion and in vivo metastasis in models of squamous cell cancer (2) phenotypic behavioral changes induced by CAFs are coordinated by BDNF-mediated TrkB signaling axis cascade that incites a pro-invasive expression profile (3) regional metastasis in mouse models of SCC is regulated in part by BDNF-TrkB signaling in the tumor microenvironment via CAFs (4) stromal-specific BDNF expression predicts outcomes for patients with SCC. Here, BDNF is linked to cancer.