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

Content Provider	Springer Nature Link
Author	Hu, Lichao Xia, Longfei Zhou, Hong Wu, Biao Mu, Yuan Wu, Ying Yan, Jinchuan
Copyright Year	2013
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, Ca$^{2+}$ 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.
Starting Page	2573
Ending Page	2581
Page Count	9
File Format	PDF
ISSN	10104283
Journal	Tumor Biology
Volume Number	34
Issue Number	5
e-ISSN	14230380
Language	English
Publisher	Springer Netherlands
Publisher Date	2013-04-25
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	Tissue factor Factor VIIa Protease-activated receptor 2 SW620 cells c-Jun/AP-1 Cancer Research
Content Type	Text
Resource Type	Article
Subject	Medicine Cancer Research

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