Arf6 regulates EGF-induced internalization of E-cadherin in breast cancer cells.

Arf6 regulates EGF-induced internalization of E-cadherin in breast cancer cells.
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Arf6 调节 EGF 诱导的乳腺癌细胞中 E-钙粘蛋白的内化

DOI:
10.1186/s12935-015-0159-3
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发表时间:
2015
影响因子:
5.8
通讯作者:
Du J
Du J
中科院分区:
医学2区
文献类型:
--
作者:
Xu R;Zhang Y;Gu L;Zheng J;Cui J;Dong J;Du J

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E-钙粘蛋白内化促进粘附连接的溶解,并促进肿瘤细胞上皮间质转化(EMT)和迁移。我们以前的研究结果表明,Arf 6在EGF刺激后对乳腺癌细胞发挥促迁移作用。尽管EGF信号刺激乳腺癌细胞的EMT,但Arf 6对EGF处理下乳腺癌细胞的E-钙粘蛋白内化的影响仍有待确定。在这里,我们发现EGF剂量依赖性地刺激MCF-7细胞的E-cadherin内化,在50 ng/ml时效果最大。同时,EGF处理显著增加Arf 6活化。Arf 6参与了E-cadherin的复合物,当Arf 6的活性增加时,更多的E-cadherin被Arf 6拉下。免疫印迹和免疫荧光检测显示,转染Arf 6-T27 N或Arf 6 siRNA的乳腺癌细胞抑制EGF诱导的E-cadherin内化。综上所述,我们的研究表明,Arf 6激活在EGF诱导的E-cadherin内化中起着潜在的作用,为Arf 6促进乳腺癌细胞转移提供了新的机制。本文的在线版本(doi:10.1186/s12935-015-0159-3)包含补充材料,可供授权用户使用。
E-cadherin internalization facilitates dissolution of adherens junctions and promotes tumor cell epithelial-mesenchymal transition (EMT) and migration. Our previous results have shown that Arf6 exerts pro-migratory action in breast cancer cells after EGF stimulation. Despite the fact that EGF signaling stimulates EMT of breast cancer cells, the effect of Arf6 on internalization of E-cadherin of breast cancer cells under EGF treatment remains to be determined. Here, we showed that EGF dose-dependently stimulated E-cadherin internalization by MCF-7 cells with the maximal effect at 50 ng/ml. Meanwhile, EGF treatment markedly increased Arf6 activation. Arf6 was involved in complexes of E-cadherin, and more E-cadherin was pulled down with Arf6 when the activity of the latter was increased. Immunoblotting and immunofluorescence assays showed that transfection breast cancer cells with Arf6-T27N or Arf6 siRNA suppressed EGF-induced E-cadherin internalization. Taken together, our study demonstrated that Arf6 activation plays a potential role in EGF-induced E-cadherin internalization, providing new mechanism underlying the effect of Arf6 on promoting breast cancer cell metastasis. The online version of this article (doi:10.1186/s12935-015-0159-3) contains supplementary material, which is available to authorized users.
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