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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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Tumor Biology

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 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.

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Acknowledgments

This work was supported by Sci-tech 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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None.

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Authors and Affiliations

  1. Department of Cardiology, Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang, Jiangsu, 212013, People’s Republic of China

    Lichao Hu, Hong Zhou & Jinchuan Yan

  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

    Lichao Hu, Longfei Xia, Hong Zhou, Biao Wu & Yuan Mu

  3. Department of Gastroenterology, Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang, Jiangsu, 212001, People’s Republic of China

    Ying Wu

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  1. Lichao Hu
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  2. Longfei Xia
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  3. Hong Zhou
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  4. Biao Wu
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  5. Yuan Mu
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  6. Ying Wu
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  7. Jinchuan Yan
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Corresponding author

Correspondence to Hong Zhou.

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Lichao Hu and Longfei Xia contributed equally to this work.

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Hu, L., Xia, L., Zhou, H. et al. TF/FVIIa/PAR2 promotes cell proliferation and migration via PKCα and ERK-dependent c-Jun/AP-1 pathway in colon cancer cell line SW620. Tumor Biol. 34, 2573–2581 (2013). https://doi.org/10.1007/s13277-013-0803-2

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  • DOI: https://doi.org/10.1007/s13277-013-0803-2

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