title: Cyr61 increases matrix metalloproteinase-3 expression and cell motility in human oral squamous cell carcinoma cells.
abstract: Oral squamous cell carcinoma (OSCC) has a striking tendency to migrate and metastasize. Cysteine-rich 61 (Cyr61), from the CCN gene family, is a secreted and matrix-associated protein, which is involved in many cellular activities such as growth and differentiation. However, the effects of Cyr61 on human OSCC cells are largely unknown. In this study, we found that Cyr61 increased the migration and the expression of matrix metalloproteinases-3 (MMP)-3 in human OSCC cells. αvβ5 or α6β1 monoclonal antibody (mAb), focal adhesion kinase (FAK) inhibitor, and mitogen-activated protein kinase (MEK) inhibitors (PD98059 and U0126) inhibited the Cyr61-induced increase of the migration and MMP-3 up-regulation of OSCC cells. Cyr61 stimulation increased the phosphorylation of FAK, MEK, and extracellular signal-regulated kinase (ERK). In addition, NF-κB inhibitors suppressed the cell migration and MMP-3 expression enhanced by Cyr61. Moreover, Cyr61 increased NF-κB luciferase activity and binding of p65 to the NF-κB element on the MMP-3 promoter. Taken together, our results indicate that Cyr61 enhances the migration of OSCC cells by increasing MMP-3 expression through the αvβ3 or α6β1 integrin receptor, FAK, MEK, ERK, and NF-κB signal transduction pathway.
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, China Medical University, Department of Pathology, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Jing-Yuan
authors.initials: JY
authors.lastname: Chuang
authors.forename: Nuo-Yi
authors.initials: NY
authors.lastname: Yu
authors.forename: I-Ping
authors.initials: IP
authors.lastname: Chiang
authors.forename: Chih-Ho
authors.initials: CH
authors.lastname: Lai
authors.forename: Chia-Der
authors.initials: CD
authors.lastname: Lin
authors.forename: Chih-Hsin
authors.initials: CH
authors.lastname: Tang
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D002070:Butadienes / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D055515:Cysteine-Rich Protein 61 / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D039121:Integrin alpha6beta1 / Q000276:immunology / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D019030:Receptors, Vitronectin / Q000276:immunology / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D002070:Butadienes; C501848:CCN1 protein, human; D055515:Cysteine-Rich Protein 61; D005419:Flavonoids; D039121:Integrin alpha6beta1; D016328:NF-kappa B; D009570:Nitriles; D019030:Receptors, Vitronectin; D051996:Transcription Factor RelA; C113580:U 0126; C064660:integrin alphaVbeta5; D051416:Focal Adhesion Protein-Tyrosine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; D019278:Matrix Metalloproteinase 3; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one