Hepsin regulates TGF? signaling via fibronectin proteolysis

ABSTRACT: Transforming growth factor beta (TGF?) is a multifunctional cytokine with a well-established role in mammary gland development and both oncogenic and tumor-suppressive functions. The extracellular matrix (ECM) indirectly regulates TGF? activity by acting as a storage compartment of latent TGF?, but how TGF? is released from the ECM via proteolytic mechanisms remains largely unknown. In this study, we demonstrate that hepsin, a type II transmembrane protease overexpressed in 70% of breast tumors, promotes canonical TGF? signaling through the release of latent TGF? from the ECM-storage compartment. Mammary glands in hepsin CRISPR knock-out mice showed reduced TGF? signaling and increased epithelial branching, accompanied by increased levels of fibronectin and latent TGF?1, while overexpressi

SUBMITTER: Denis Belitskin 

PROVIDER: S-SCDT-EMBOR-2021-52532V1 | biostudies-other |

REPOSITORIES: biostudies-other