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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 ?6?1 integrin expression. A neutralizing ?6?1 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 ?6?1 integrin levels and higher grades in patients. These findings can potentially serve as biomarker and therapeutic approach for controlling chondrosarcoma metastasis.

SUBMITTER: Chen JC

PROVIDER: S-EPMC4484467 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Amphiregulin enhances alpha6beta1 integrin expression and cell motility in human chondrosarcoma cells through Ras/Raf/MEK/ERK/AP-1 pathway.

Chen Jui-Chieh JC Chen Yu-Ju YJ Lin Chih-Yang CY Fong Yi-Chin YC Hsu Chin-Jung CJ Tsai Chun-Hao CH Su Jen-Liang JL Tang Chih-Hsin CH

Oncotarget 20150501 13

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. ...[more]

PMID: 25825984

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