HAHI 2 ACTIVATOR

Among them, pericellular proteases receive attention because of their pivotal roles in the degradation of extracellular matrix (ECM), and the activation of cell-surface growth factors. There are many factors or mechanisms involved in cancer cell invasion and metastasis, including growth factors, EpithelialвЂ“Mesenchymal transition (EMT), and protease system. Currently, there is no effective therapy available for metastatic PCa patients.ДЇor cancer metastasis, primary tumor cells need to break down the local barrier, gain a movement ability or penetrate blood vessels, and eventually spread out and grow in distant tissues or organs. Metastasis is the major cause for the morbidity and mortality of PCa patients. PCa progression is a slow process, which undergoes several stages including prostatic intraepithelial neoplasia, adenocarcinoma, and metastasis. Prostate cancer (PCa) is one of the most frequently diagnosed malignancies worldwide, and the second leading cause of cancer death in males in USA. In summary, the results together indicate that HAI-2 can function as a cognate inhibitor for TMPRSS2 in human prostate cancer cells and may serve as a potential factor to suppress TMPRSS2-mediated malignancy. In orthotopic xenograft animal model, TMPRSS2 overexpression promoted prostate cancer metastasis, and HAI-2 overexpression efficiently blocked TMPRSS2-induced metastasis. We further determined that the expression levels of TMPRSS2 were inversely correlated with HAI-2 levels during prostate cancer progression. In addition, HAI-2 overexpression could suppress the induction effect of TMPRSS2 on pro-HGF activation, extracellular matrix degradation and prostate cancer cell invasion.

Both KD1 and KD2 domain of HAI-2 showed comparable inhibitory effects on TMPRSS2 proteolytic activity. The immunofluorescence images further showed that TMPRSS2 was co-localized to HAI-2. Moreover, the recombinant HAI-2 proteins exhibited a better inhibitory effect on TMPRSS2 proteolytic activity than HAI-1, and recombinant HAI-2 proteins had a high affinity to form a complex with TMPRSS2.

HAHI 2 ACTIVATOR

To identify the cognate inhibitor of TMPRSS2, in this study, we applied co-immunoprecipitation and LC/MS/MS analysis and isolated hepatocyte growth factor activator inhibitors (HAIs) to be potential inhibitor candidates for TMPRSS2. A serine protease physiologically often comes together with a cognate inhibitor for execution of proteolytically biologic function however, TMPRSS2вЂ™s cognate inhibitor is still elusive. TMPRSS2 is an important membrane-anchored serine protease involved in human prostate cancer progression and metastasis.

Hahi 2