Identification of a small-molecule ligand of β-arrestin1 as an inhibitor of stromal fibroblast cell migration accelerated by cancer cells.

ABSTRACT: Stromal fibroblasts, which occupy a major portion of the tumor microenvironment, play an important role in cancer metastasis. Thus, targeting of these fibroblasts activated by cancer cells (carcinoma-associated fibroblasts; CAFs) might aid in the improved treatment of cancer metastasis. NIH3T3 fibroblasts cocultured with MCF7 cells displayed enhanced migration compared to NIH3T3 fibroblasts cultured alone. We used this system to identify the small-molecule inhibitors responsible for their enhanced migration, a characteristic of CAFs. We selected β-arrestin1, which showed high expression in cocultured cells, as a molecular target for such inhibitors. Cofilin, a protein downstream of β-arrestin1, is activated/dephosphorylated in this condition. The small-molecule ligands of β-arrestin1 obtai

SUBMITTER: Suvarna K 

PROVIDER: S-EPMC5852355 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature