title: Amphiregulin enhances alpha6beta1 integrin expression and cell motility in human chondrosarcoma cells through Ras/Raf/MEK/ERK/AP-1 pathway.
abstract: Chondrosarcoma is a malignant tumor that produces cartilage matrix. The most lethal aspect is its metastatic property. We demonstrated that amphiregulin (AR) is significantly upregulated in highly aggressive cells. AR silencing markedly suppressed cell migration. Exogenous AR markedly increased cell migration by transactivation of α6β1 integrin expression. A neutralizing α6β1 integrin antibody can abolish AR-induced cell motility. Knockdown of AR inhibits metastasis of cells to the lung in vivo. Furthermore, elevated AR expression is positively correlated with α6β1 integrin levels and higher grades in patients. These findings can potentially serve as biomarker and therapeutic approach for controlling chondrosarcoma metastasis.
authors.affiliation: Department of Biochemical Science and Technology, National Chiayi University, Chiayi, Taiwan.|Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.|National Institute of Cancer Research, National Health Research Institutes, Miaoli County, Taiwan.
authors.forename: Jui-Chieh
authors.initials: JC
authors.lastname: Chen
authors.affiliation: School of Pharmacy, China Medical University, Taichung, Taiwan.
authors.forename: Yu-Ju
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Lin
authors.affiliation: School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan.|Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Yi-Chin
authors.initials: YC
authors.lastname: Fong
authors.affiliation: School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan.|Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Chin-Jung
authors.initials: CJ
authors.lastname: Hsu
authors.affiliation: Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan.|Department of Medicine and Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Chun-Hao
authors.initials: CH
authors.lastname: Tsai
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Miaoli County, Taiwan.|Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan.|Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan.|Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan.
authors.forename: Jen-Liang
authors.initials: JL
authors.lastname: Su
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.|Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan.|Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Chih-Hsin
authors.initials: CH
authors.lastname: Tang
mesh_terms: D066258:Amphiregulin; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002813:Chondrosarcoma / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000556:secondary; D004305:Dose-Response Relationship, Drug; D066255:EGF Family of Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D039121:Integrin alpha6beta1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000201:enzymology / Q000517:prevention & control / Q000556:secondary; D048369:MAP Kinase Kinase 1 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008819:Mice, Nude; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D034622:RNA Interference; D015398:Signal Transduction; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D023041:Xenograft Model Antitumor Assays; D048490:raf Kinases / Q000235:genetics / Q000378:metabolism*; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C587848:AREG protein, human; D066258:Amphiregulin; D000906:Antibodies; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D066255:EGF Family of Proteins; D039121:Integrin alpha6beta1; D018808:Transcription Factor AP-1; D048490:raf Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human; D018631:ras Proteins
keywords: amphiregulin; cell migration; chondrosarcoma; integrin
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