title: Endothelin-1 promotes MMP-13 production and migration in human chondrosarcoma cells through FAK/PI3K/Akt/mTOR pathways.
abstract: Tumor malignancy is associated with several cellular properties including proliferation and ability to metastasize. Endothelin-1 (ET-1) the most potent vasoconstrictor plays a crucial role in migration and metastasis of human cancer cells. We found that treatment of human chondrosarcoma (JJ012 cells) with ET-1 increased migration and expression of matrix metalloproteinase (MMP)-13. ET-1-mediated cell migration and MMP-13 expression were reduced by pretreatment with inhibitors of focal adhesion kinase (FAK), phosphatidylinositol 3-kinase (PI3K), Akt, and mammalian target of rapamycin (mTOR), as well as the NF-κB inhibitor and the IκB protease inhibitor. In addition, ET-1 treatment induced phosphorylation of FAK, PI3K, AKT, and mTOR, and resulted in increased NF-κB-luciferase activity that was inhibited by a specific inhibitor of PI3K, Akt, mTOR, and NF-κB cascades. Taken together, these results suggest that ET-1 activated FAK/PI3K/AKT/mTOR, which in turn activated IKKα/β and NF-κB, resulting in increased MMP-13 expression and migration in human chondrosarcoma cells.
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University and Hospital, Taichung, Taiwan.
authors.forename: Min Huan
authors.initials: MH
authors.lastname: Wu
authors.forename: Jeng-Fan
authors.initials: JF
authors.lastname: Lo
authors.forename: Chia-Hua
authors.initials: CH
authors.lastname: Kuo
authors.forename: James A
authors.initials: JA
authors.lastname: Lin
authors.forename: Yueh-Min
authors.initials: YM
authors.lastname: Lin
authors.forename: Li-Mien
authors.initials: LM
authors.lastname: Chen
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai
authors.forename: Chang-Hai
authors.initials: CH
authors.lastname: Tsai
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
authors.forename: Chih-Hsin
authors.initials: CH
authors.lastname: Tang
mesh_terms: D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002813:Chondrosarcoma / Q000378:metabolism / Q000473:pathology; D019332:Endothelin-1 / Q000008:administration & dosage / Q000378:metabolism*; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D019332:Endothelin-1; D016328:NF-kappa B; D000081082:Phosphoinositide-3 Kinase Inhibitors; C546842:MTOR protein, human; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D051550:I-kappa B Kinase; D053509:Matrix Metalloproteinase 13