Inhibiting Tumor Fibrosis and Actomyosin through GPCR activation

Abstract

Myofibroblasts produce desmoplastic stroma around tumors and have emerged as therapeutic targets in pancreatic ductal adenocarcinoma (PDAC) and other cancers. Differentiation of pancreatic stellate cells (PSCs) into myofibroblasts is inhibited by the estrogen-receptor modulator, tamoxifen, which activates a G-protein-coupled receptor (GPCR) for estrogen (GPER). This negatively regulates actomyosin contractility and downstream mechanosensitive signaling to profoundly alter the tumor microenvironment, which appears less fibrotic, less immunosuppressive, and more vascularized.