Hepsin promotes breast tumor growth signaling via TGF beta-EGFR axis

Background: Hepsin, a type II transmembrane serine protease encoded by HPN gene, is commonly overexpressed in prostate and breast cancer. Hepsin protein stabilized Ras-MAPK pathway signaling, downstream, this regulates the degradation of extracellular matrix components activates growth factor pathways, including hepatocyte transforming (TGF) beta pathway. The significance hepsin-dependent signaling on cell proliferation tumor still partially unclear. Material methods: We used engineered cancer lines, WAP-Myc; Hpn−/− mouse model, patient-derived explant cultures from tumors to illuminate role hepsin growth. Results: made orthotopic transplantation into syngeneic wild-type recipient mice isolated mammary cells. resulting had decreased size both primary metastatic site comparison derived Hpn+/+ This was accompanied downregulation total epidermal receptor (EGFR) levels as well reduction EGFR TGF signaling. In addition, we showed that 3D culture overexpression induced 1 signaling-dependent proliferation, while PDECs treated with inhibiting antibodies small molecules activity less marker expression. Conclusions: study demonstrates for regulator through warranting consideration potential indirect upstream target therapeutic inhibition pathways No conflict interest.