title: Activation of PAR2 or/and TLR4 promotes SW620 cell proliferation and migration via phosphorylation of ERK1/2.
abstract: Protease-activated receptor 2 (PAR2) is a G-protein-coupled receptor and its activation has been associated with the pathogenetic progress in certain cancers. Toll-like receptor 4 (TLR4), one member of Toll-like receptors family, is mainly contributed to the innate immune response. However, recent studies have shown that TLR4 is aberrantly expressed in various types of carcinomas and may correlate with tumor progression. Previously, we reported that PAR2 could be expressed in human colon cancer cell line (SW620) and its activation by some stimulants was able to facilitate cell proliferation and migration. In our recent preliminary experiment, it was found that SW620 cells also had TLR4 expression. Thus, we considered that PAR2 and TLR4 could have some collaborative roles in SW620 cells. In the current study, the cross-inducible expression of PAR2 and TLR4 on SW620 cells was investigated, and the functional roles of their activation on the behavior of SW620 cells were evaluated. It was found that activation of PAR2 with PAR2-AP (PAR2 agonist, 100 μM) enhanced TLR4 releasement and vice versa. The activation of PAR2 or TLR4 (with LPS, 100 ng/ml) could promote SW620 cell proliferation and migration, and the phosphorylation of ERK1/2 but not p38MAPK, as well as the expression of interleukin 8 (IL-8) and tissue factor (TF). Whereas the caspase-7 expression was decreased under PAR2 or TLR4 activation. Furthermore, ERK1/2 inhibitor (U0126, at 10 μM) could intervene in all regulating effects of PAR2 or/and TLR4. Collectively, this study demonstrated that both PAR2 and TLR4 activation on SW620 cells can trigger the phosphorylation of ERK1/2, regulate the expression of IL-8, TF and caspase-7, thereby promote the proliferation and migration of cells.
authors.affiliation: Department of Clinical Laboratory and Hematology, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu 212013, PR China.
authors.forename: Baocheng
authors.initials: B
authors.lastname: Zhou
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.forename: Shucai
authors.initials: S
authors.lastname: Ling
authors.forename: Donglin
authors.initials: D
authors.lastname: Guo
authors.forename: Yihong
authors.initials: Y
authors.lastname: Yan
authors.forename: Fang
authors.initials: F
authors.lastname: Zhou
authors.forename: Ying
authors.initials: Y
authors.lastname: Wu
mesh_terms: D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism* / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D020239:Receptor Cross-Talk / Q000187:drug effects / Q000502:physiology; D044464:Receptor, PAR-2 / Q000819:agonists* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000819:agonists* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D008070:Lipopolysaccharides; D009842:Oligopeptides; D044464:Receptor, PAR-2; D051197:Toll-Like Receptor 4; C515807:seryl-leucyl-isoleucyl-glycyl-lysyl-valinamide; D048052:Mitogen-Activated Protein Kinase 3