TF/FVIIa/PAR2 promotes cell proliferation and migration via PKCα and ERK-dependent c-Jun/AP-1 pathway in colon cancer cell line SW620

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• 作者：Lichao Hu (1) (2)
  Longfei Xia (2)
  Hong Zhou (1) (2)
  Biao Wu (2)
  Yuan Mu (2)
  Ying Wu (3)
  Jinchuan Yan (1)
  
• 关键词：Tissue factor ; Factor VIIa ; Protease ; activated receptor 2 ; SW620 cells ; c ; Jun/AP ; 1
• 刊名：Tumor Biology
• 出版年：2013
• 出版时间：October 2013
• 年：2013
• 卷：34
• 期：5
• 页码：2573-2581
• 全文大小：
• 作者单位：Lichao Hu (1) (2)
  Longfei Xia (2)
  Hong Zhou (1) (2)
  Biao Wu (2)
  Yuan Mu (2)
  Ying Wu (3)
  Jinchuan Yan (1)
  
  1. Department of Cardiology, Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang, Jiangsu, 212013, People’s Republic of China
  2. Department of Clinical Laboratory and Hematology, School of Medical Science and Laboratory Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu, 212001, People’s Republic of China
  3. Department of Gastroenterology, Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang, Jiangsu, 212001, People’s Republic of China
  
• ISSN：1423-0380

文摘

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 protease-activated 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 protein-1 (AP-1) subunit c-Jun. The results revealed that PAR2-AP and FVIIa could upregulate c-Jun expression and c-Jun phosphorylation in SW620 cells in a time-dependent manner. The effect of FVIIa was significantly blocked by anti-TF and anti-PAR2 antibodies. Protein kinase Cα (PKCα) inhibitor safingol and extracellular signal-regulated kinase 1 and 2 (ERK1/2) inhibitor U0126 abrogated the activation of c-Jun. In contrast, Ca2+ chelators EGTA and thapsigargin, and p38MAPK inhibitor SB203580 had no effect. Suppression of c-Jun/AP-1 activation using a natural inhibitor curcumin decreased the expression of caspase-3, MMP-9, and TF, as well as the proliferation and migration of SW620 cells induced by PAR2-AP or FVIIa. Collectively, our findings suggest that c-Jun/AP-1 activation is required for TF/FVIIa/PAR2-induced SW620 cell proliferation and migration. PKCα and ERK1/2 are located upstream of c-Jun/AP-1 in this signaling pathway. Pharmacological inhibition of this pathway might be a novel strategy for colon cancer therapy.