Amphiregulin enhances alpha6beta1 integrin expression and cell motility in human chondrosarcoma cells through Ras/Raf/MEK/ERK/AP-1 pathway
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Jui-Chieh Chen1,2,3, Yu-Ju Chen4, Chih-Yang Lin2, Yi-Chin Fong5,6, Chin-Jung Hsu5,6, Chun-Hao Tsai6,7, Jen-Liang Su3,8,9,10, Chih-Hsin Tang2,8,11
1Department of Biochemical Science and Technology, National Chiayi University, Chiayi, Taiwan
2Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan
3National Institute of Cancer Research, National Health Research Institutes, Miaoli County, Taiwan
4School of Pharmacy, China Medical University, Taichung, Taiwan
5School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan
6Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan
7Department of Medicine and Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan
8Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan
9Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan
10Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan
11Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan
Chih-Hsin Tang, e-mail: [email protected]
Jen-Liang Su, e-mail: [email protected]
Keywords: chondrosarcoma, amphiregulin, integrin, cell migration
Received: January 06, 2015 Accepted: February 16, 2015 Published: March 18, 2015
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.
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