Authors: Lichao Hu Longfei Xia Hong Zhou Biao Wu Yuan Mu Ying Wu Jinchuan Yan
Publish Date: 2013/04/25
Volume: 34, Issue: 5, Pages: 2573-2581
Abstract
Our previous study has demonstrated that tissue factor–factor VIIa TF/FVIIa complex promotes the proliferation and migration of colon cancer cell line SW620 through the activation of proteaseactivated receptor 2 PAR2 In the current study the underlying molecular mechanisms of TF/FVIIa/PAR2 signaling in SW620 cells were further explored with the focus on the role of activator protein1 AP1 subunit cJun The results revealed that PAR2AP and FVIIa could upregulate cJun expression and cJun phosphorylation in SW620 cells in a timedependent manner The effect of FVIIa was significantly blocked by antiTF and antiPAR2 antibodies Protein kinase Cα PKCα inhibitor safingol and extracellular signalregulated kinase 1 and 2 ERK1/2 inhibitor U0126 abrogated the activation of cJun In contrast Ca2+ chelators EGTA and thapsigargin and p38MAPK inhibitor SB203580 had no effect Suppression of cJun/AP1 activation using a natural inhibitor curcumin decreased the expression of caspase3 MMP9 and TF as well as the proliferation and migration of SW620 cells induced by PAR2AP or FVIIa Collectively our findings suggest that cJun/AP1 activation is required for TF/FVIIa/PAR2induced SW620 cell proliferation and migration PKCα and ERK1/2 are located upstream of cJun/AP1 in this signaling pathway Pharmacological inhibition of this pathway might be a novel strategy for colon cancer therapyThis work was supported by Scitech Innovation Team of Jiangsu Province no LJ201116 and Key Laboratory of Cardiovascular disease of Zhenjiang SS2012002 to Jinchuan Yan Natural Science Foundation of Jiangsu Province no BK2010336 to Ying Wu and Student’s Scientific Research of Jiangsu University no Y11A183 to Lichao Hu
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