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

双调蛋白通过 Ras/Raf/MEK/ERK/AP-1 通路增强人软骨肉瘤细胞中 alpha6beta1 整合素的表达和细胞迁移能力

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作者:Jui-Chieh Chen, Yu-Ju Chen, Chih-Yang Lin, Yi-Chin Fong, Chin-Jung Hsu, Chun-Hao Tsai, Jen-Liang Su, Chih-Hsin Tang1

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.

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