Tissue kallikrein promotes prostate cancer cell migration and invasion via a protease-activated receptor-1-dependent signaling pathway
-
Lin Gao
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
Articles in the same Issue
- Guest Editorial
- Highlight: Of Systems and Structures
- HIGHLIGHT: STRUCTURAL SYSTEMS BIOLOGY
- Converging on the function of intrinsically disordered nucleoporins in the nuclear pore complex
- Towards molecular systems biology of gene transcription and regulation
- Small-angle X-ray and neutron scattering as a tool for structural systems biology
- The type III secretion injectisome, a complex nanomachine for intracellular ‘toxin’ delivery
- Structural insights into the evolution of the adaptive immune system: the variable lymphocyte receptors of jawless vertebrates
- The XPD helicase: XPanDing archaeal XPD structures to get a grip on human DNA repair
- Decoding transcription and microRNA-mediated translation control in Drosophila development
- Human SepSecS or SLA/LP: selenocysteine formation and autoimmune hepatitis
- PROTEIN STRUCTURE AND FUNCTION
- The rhodanese RhdA helps Azotobacter vinelandii in maintaining cellular redox balance
- MEMBRANES, LIPIDS, GLYCOBIOLOGY
- The membrane-bound bile acid receptor TGR5 (Gpbar-1) is localized in the primary cilium of cholangiocytes
- CELL BIOLOGY AND SIGNALING
- miR-221/222 suppression protects against endoplasmic reticulum stress-induced apoptosis via p27Kip1- and MEK/ERK-mediated cell cycle regulation
- Tissue kallikrein promotes prostate cancer cell migration and invasion via a protease-activated receptor-1-dependent signaling pathway
- Sprouty4 levels are increased under hypoxic conditions by enhanced mRNA stability and transcription
- PROTEOLYSIS
- Degradation of human kininogens with the release of kinin peptides by extracellular proteinases of Candida spp.
- NOVEL TECHNIQUES
- Detection of breast cancer-related antigens through cDNA phage-displayed protein microarray
Articles in the same Issue
- Guest Editorial
- Highlight: Of Systems and Structures
- HIGHLIGHT: STRUCTURAL SYSTEMS BIOLOGY
- Converging on the function of intrinsically disordered nucleoporins in the nuclear pore complex
- Towards molecular systems biology of gene transcription and regulation
- Small-angle X-ray and neutron scattering as a tool for structural systems biology
- The type III secretion injectisome, a complex nanomachine for intracellular ‘toxin’ delivery
- Structural insights into the evolution of the adaptive immune system: the variable lymphocyte receptors of jawless vertebrates
- The XPD helicase: XPanDing archaeal XPD structures to get a grip on human DNA repair
- Decoding transcription and microRNA-mediated translation control in Drosophila development
- Human SepSecS or SLA/LP: selenocysteine formation and autoimmune hepatitis
- PROTEIN STRUCTURE AND FUNCTION
- The rhodanese RhdA helps Azotobacter vinelandii in maintaining cellular redox balance
- MEMBRANES, LIPIDS, GLYCOBIOLOGY
- The membrane-bound bile acid receptor TGR5 (Gpbar-1) is localized in the primary cilium of cholangiocytes
- CELL BIOLOGY AND SIGNALING
- miR-221/222 suppression protects against endoplasmic reticulum stress-induced apoptosis via p27Kip1- and MEK/ERK-mediated cell cycle regulation
- Tissue kallikrein promotes prostate cancer cell migration and invasion via a protease-activated receptor-1-dependent signaling pathway
- Sprouty4 levels are increased under hypoxic conditions by enhanced mRNA stability and transcription
- PROTEOLYSIS
- Degradation of human kininogens with the release of kinin peptides by extracellular proteinases of Candida spp.
- NOVEL TECHNIQUES
- Detection of breast cancer-related antigens through cDNA phage-displayed protein microarray
