Miao, J., Mu, D., Ergel, B., Singavarapu, R., Duan, Z., Powers, S., Oliva, E., Orsulic, S. (November 2008) Hepsin colocalizes with desmosomes and induces progression of ovarian cancer in a mouse model. Int J Cancer, 123 (9). pp. 2041-7.
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.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | Animals Cell Line, Tumor Cell Proliferation Desmosomes/*chemistry Disease Models, Animal Disease Progression Female Hepatocyte Growth Factor/analysis/physiology Humans Mice Mice, Inbred C57BL Mice, Nude Ovarian Neoplasms/*pathology Serine Endopeptidases/analysis/*physiology |
| Subjects: | diseases & disorders > cancer diseases & disorders organism description > animal organism description > animal > mammal > rodent > mouse diseases & disorders > cancer > cancer types > ovarian cancer diseases & disorders > cancer > cancer types |
| CSHL Authors: | |
| Communities: | CSHL labs > Powers lab |
| Depositing User: | Matt Covey |
| Date: | 1 November 2008 |
| Date Deposited: | 26 Feb 2013 20:26 |
| Last Modified: | 26 Feb 2013 20:26 |
| PMCID: | PMC2653430 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/27541 |
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