Involvement of PKCα activation in TF/VIIa/PAR2-induced proliferation, migration, and survival of colon cancer cell SW620.

Abstract

Our previous study has demonstrated that protease-activated receptor 2 (PAR2) activation mediated by tissue factor (TF)/VIIa complex triggers the ERK1/2/NF-κB signaling pathway, which further contributes to the proliferation and migration of colon cancer cell line SW620. However, the detailed mechanisms remain unclear. This study was to investigate whether protein kinase Cα (PKCα) is involved in these events and the possible mechanism. The results revealed that PAR2-activating peptide or VIIa could induce time-dependent upregulation of PKCα phosphorylation in SW620 cells and PKCα translocation from the cytoplasm to the perinuclear region and nucleus. The activation of PKCα was sufficient to induce ERK1/2 and NF-κB phosphorylation. The VIIa effect was obviously blocked by both anti-TF and anti-PAR2 antibodies. The PKCα inhibitor, safingol, inhibited ERK1/2 phosphorylation and NF-κB activation that is induced by VIIa and abrogated the enhanced proliferation, migration, and survival of SW620 cells by VIIa treatment. Both safingol and PDTC (NF-κB inhibitor) could apparently rescue the effects of VIIa on expression of MMP-9, caspase-3, TF, and Bcl-2/bax in SW620 cells. Collectively, the data in this study suggest that TF/VIIa/PAR2-induced SW620 cell proliferation, migration, and survival are ascribed to the activation of PKCα, and these effects are achieved through PKCα downstream signaling pathways, ERK1/2 and NF-κB.

• Authors: Biao Wu, Hong Zhou, Lichao Hu, Yuan Mu, Ying Wu
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 34 Issue 2 Pg. 837-46 (Apr 2013) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 23233043 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• NF-kappa B
• RNA, Messenger
• Receptor, PAR-2
• Thromboplastin
• Protein Kinase C-alpha
• Factor VIIa

Topics

• Apoptosis
• Blotting, Western
• Cell Adhesion
• Cell Movement
• Cell Proliferation
• Colonic Neoplasms (genetics, metabolism, pathology)
• Factor VIIa (genetics, metabolism)
• Flow Cytometry
• Fluorescent Antibody Technique
• Humans
• MAP Kinase Signaling System
• NF-kappa B (genetics, metabolism)
• Protein Kinase C-alpha (antagonists & inhibitors, genetics, metabolism)
• RNA, Messenger (genetics)
• Real-Time Polymerase Chain Reaction
• Receptor, PAR-2 (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Thromboplastin (genetics, metabolism)
• Tumor Cells, Cultured