Title
Tissue kallikrein promotes prostate cancer cell migration and invasion via a protease-activated receptor-1-dependent signaling pathway
Abbreviated Journal Title
Biol. Chem.
Keywords
invasion; kinin B2 receptor; migration; prostate cancer; protease-activated receptor; tissue kallikrein; GROWTH-FACTOR RECEPTOR; BRADYKININ B-2 RECEPTOR; KERATINOCYTE MIGRATION; URINARY KALLIKREIN; CARCINOMA-CELLS; KININ FORMATION; IV COLLAGENASE; TUMOR-GROWTH; TRANSACTIVATION; EGF; Biochemistry & Molecular Biology
Abstract
We recently demonstrated that tissue kallikrein (TK) promotes keratinocyte migration through activation of protease-activated receptor-1 (PAR(1)) and transactivation of the epidermal growth factor receptor (EGFR). In this study, we investigated the potential role of PAR, 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 PAR, 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, EGER and extracellular signal-regulated kinase (ERK). Moreover, TK stimulates ERK phosphorylation, which is inhibited by an EGER antagonist. Additionally, TK but not kinin stimulates DU145 cell proliferation through activation of the kinin B2 receptor, but not PAR, and EGFR. These results indicate differential signaling pathways mediated by TK in promoting prostate cancer cell migration and invasion via PAR, activation, and proliferation via kinin B2 receptor stimulation.
Journal Title
Biological Chemistry
Volume
391
Issue/Number
7
Publication Date
1-1-2010
Document Type
Article
Language
English
First Page
803
Last Page
812
WOS Identifier
ISSN
1431-6730
Recommended Citation
"Tissue kallikrein promotes prostate cancer cell migration and invasion via a protease-activated receptor-1-dependent signaling pathway" (2010). Faculty Bibliography 2010s. 7053.
https://stars.library.ucf.edu/facultybib2010/7053
Comments
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