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

Amphiregulin enhances alpha6beta1 integrin expression and cell motility in human chondrosarcoma cells through Ras/Raf/MEK/ERK/AP-1 pathway.
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DOI:
10.18632/oncotarget.3397
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发表时间:
2015-05-10
期刊:
影响因子:
--
通讯作者:
Tang CH
Tang CH
中科院分区:
其他
文献类型:
--
作者:
Chen JC;Chen YJ;Lin CY;Fong YC;Hsu CJ;Tsai CH;Su JL;Tang CH

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软骨肉瘤是一种产生软骨基质的恶性肿瘤。最致命的方面是它的转移性。我们证明了双调节蛋白(AR)在高度侵袭性细胞中显著上调。AR沉默明显抑制细胞迁移。外源性AR通过反式激活α-6-β-1整合素表达,显著促进细胞迁移。中和性α6β1整合素抗体可阻断AR诱导的细胞运动。在体内,AR基因的敲除可抑制细胞向肺的转移。此外,AR表达升高与α-6-β-1整合素水平及肿瘤分级呈正相关。这些发现可能成为控制软骨肉瘤转移的生物标志物和治疗方法。
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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