Cancer-associated fibroblast-secreted collagen triple helix repeat containing-1 promotes breast cancer cell migration, invasiveness and epithelial-mesenchymal transition by activating the Wnt/β-catenin pathway.

Cancer-associated fibroblasts (CAFs) are continuously activated and are one of the most important cellular components of the tumor matrix. The role of CAFs in the tumor microenvironment has been widely recognized. However, the underlying molecular mechanism by which CAFs promote tumor characteristics in breast cancer (BC) remains poorly understood. The aim of the present study was to investigate the potential mechanisms and the possible pathways of collagen triple helix repeat containing-1 (CTHRC1) in the epithelial-mesenchymal transition (EMT) of BC cells. The level of CTHRC1 in BC tissues was found to be higher than that in adjacent-normal tissues. CAFs isolated from BC tissues secreted significantly greater amounts of CTHRC1 than normal fibroblasts. Furthermore, CAFs promoted the migration, invasiveness and EMT of BC cells by secreting CTHRC1, which activates the Wnt/β-catenin signaling pathway. However, the use of neutralizing antibodies towards CTHRC1, or the specific inhibitor Dickkopf-1, to inhibit the Wnt/β catenin pathway significantly alleviated the CAF-induced malignant phenotypes of BC cells. Collectively, the data indicate that CAFs in the tumor microenvironment promote BC cell malignant behaviors via the CTHRC1/Wnt/β-catenin signaling pathway. Furthermore, weakening CAF-BC cell communication by suppressing CTHRC1 expression may be a novel strategy for treating BC.