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. Author manuscript; available in PMC: 2016 Sep 1.
Published in final edited form as: Biol Chem. 2016 Sep 1;397(9):815–826. doi: 10.1515/hsz-2016-0131

Figure 1. Simple schematic representation showing two TTSPs, matriptase and hepsin, that are localized on the cell surface of cancer cells.

Figure 1

Proteolytic cleavage of stromal cell-secreted pro-HGF to signaling competent HGF elicits the HGF/c-Met pro-oncogenic signaling pathway in cancer. Matriptase activates pro-HGF in squamous cell carcinomas (Szabo et al., 2011) and in breast cancer in vivo (Zoratti et al., 2015). Hepsin has been reported to activate pro-HGF in immortalized mammary epithelial cells (Tervonen et al., 2016) and in prostate cancer cells (Owen et al., 2010). TMPRSS2 (not shown) has been proposed to activate pro-HGF in prostate cancer (Lucas et al., 2014). The development of inhibitors of matriptase, hepsin or TMPRSS2 may represent alternatives to existing receptor tyrosine kinase inhibitors to impair invasion, proliferation and metastasis. Diagnostic imaging of protease activity is also being explored using, e.g. specific antibodies and activity-based probes.