title: Hepsin colocalizes with desmosomes and induces progression of ovarian cancer in a mouse model.
abstract: Hepsin is a serine protease that is widely expressed in different tissues and cell types, most prominently in the normal liver and kidney. Overexpression of hepsin has been associated with prostate cancers, ovarian cancers and renal cell carcinomas. The physiological functions of hepsin in normal tissues and tumors are poorly understood. To gain insight into its function in ovarian cancer, we analyzed the expression and subcellular localization of hepsin protein in ovarian cancer cell lines and tumors. We showed that the membrane-associated hepsin protein is present at desmosomal junctions, where it colocalizes with its putative proteolytic substrate hepatocyte growth factor. Consistent with the growing evidence that desmosomal junctions and their constituents play a role in cancer progression, we demonstrated that overexpression of hepsin promotes ovarian tumor growth in a mouse model. The ability of ectopic hepsin to induce tumor growth in mice is abrogated by the mutation of 3 critical residues in the catalytic domain, thus implicating the enzymatic activity of hepsin in promoting tumor progression.
authors: Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA.
authors: Jiangyong
authors: J
authors: Miao
authors: David
authors: D
authors: Mu
authors: Burce
authors: B
authors: Ergel
authors: Rajasekhar
authors: R
authors: Singavarapu
authors: Zhenfeng
authors: Z
authors: Duan
authors: Scott
authors: S
authors: Powers
authors: Esther
authors: E
authors: Oliva
authors: Sandra
authors: S
authors: Orsulic
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003896:Desmosomes / Q000737:chemistry*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D017228:Hepatocyte Growth Factor / Q000032:analysis / Q000502:physiology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000473:pathology*; D012697:Serine Endopeptidases / Q000032:analysis / Q000502:physiology*
chemical_list: D017228:Hepatocyte Growth Factor; D012697:Serine Endopeptidases; C055645:hepsin