Title

Tissue Kallikrein Promotes Prostate Cancer Cell Migration And Invasion Via A Protease-Activated Receptor-1-Dependent Signaling Pathway

Keywords

invasion; kinin B2 receptor; migration; prostate cancer; protease-activated receptor; tissue kallikrein

Abstract

We recently demonstrated that tissue kallikrein (TK) promotes keratinocyte migration through activation of protease-activated receptor-1 (PAR1) and transactivation of the epi-dermal growth factor receptor (EGFR). In this study, we investigated the potential role of PAR1 in mediating the effect of TK on cancer cell migration, invasion and proliferation. Our results show that TK promotes DU145 prostate cancer cell migration in a concentration-dependent manner, but has no effect on A549 lung cancer cells. Active TK markedly increases DU145 cell migration and invasion, which are blocked by aprotinin but minimally affected by icatibant; kinin treatment has little effect. TK-induced cell migration and invasion are abolished by inhibition of PAR1 using a pharmacological inhibitor or RNA interference. The effect of TK on cell migration and invasion are also blocked by inhibitors of protein kinase C, c-Src, matrix metalloproteinase, EGFR and extracellular signal-regulated kinase (ERK). Moreover, TK stimulates ERK phosphorylation, which is inhibited by an EGFR antagonist. Additionally, TK but not kinin stimulates DU145 cell proliferation through activation of the kinin B2 receptor, but not PAR1 and EGFR. These results indicate differential signaling pathways mediated by TK in promoting prostate cancer cell migration and invasion via PAR1 activation, and proliferation via kinin B2 receptor stimulation. © 2010 by Walter de Gruyter Berlin New York.

Publication Date

7-1-2010

Publication Title

Biological Chemistry

Volume

391

Issue

7

Number of Pages

803-812

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1515/BC.2010.084

Socpus ID

77954572813 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/77954572813

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