Regulation of vimentin by SIP1 in human epithelial breast tumor cells
Regulation of vimentin by SIP1 in human epithelial breast tumor cells
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DOI：
10.1038/sj.onc.1209511
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发表时间：
2006-08-17
期刊：
影响因子：
8
通讯作者：
Gilles, C.
中科院分区：
文献类型：
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作者：
Bindels, S.;Mestdagt, M.;Gilles, C.
在正常和病理条件下，Smad相互作用蛋白-1(SIP1；ZEB2)的表达和波形蛋白的从头表达经常参与EMTs的转化。在本研究中，我们研究了SIP1在乳腺肿瘤细胞迁移和侵袭的EMT过程中对Vimentin的调节作用。对几个表现出不同侵袭性的乳腺肿瘤细胞系进行检测，发现SIP1和Vimentin仅在侵袭性细胞系中表达。此外，利用人乳腺MCF10A细胞的细胞迁移模型，我们发现SIP1在Vimentin阳性的迁移细胞中被特异性地诱导。此外，在Boyden小室实验中，SIP1基因在MCF10A细胞中的表达增加了Vimentin在mRNA和蛋白水平的表达，并增强了细胞的迁移能力。相反，通过RNAi策略抑制SIP1在BT-549细胞和MCF10A细胞中的表达减少了波形蛋白的表达。我们还发现，SIP1没有激活TOP-Flash报告系统，提示β-连环蛋白/TCF通路不参与SIP1对波形蛋白的调节。因此，我们的结果表明SIP1参与了与乳腺肿瘤细胞迁移相关的EMT中观察到的波形蛋白的调节，这一途径可能有助于乳腺癌的转移进展。
The expression of Smad interacting protein-1 (SIP1; ZEB2) and the de novo expression of vimentin are frequently involved in epithelial-to-mesenchymal transitions (EMTs) under both normal and pathological conditions. In the present study, we investigated the potential role of SIP1 in the regulation of vimentin during the EMT associated with breast tumor cell migration and invasion. Examining several breast tumor cell lines displaying various degrees of invasiveness, we found SIP1 and vimentin expression only in invasive cell lines. Also, using a model of cell migration with human mammary MCF10A cells, we showed that SIP1 is induced specifically in vimentin-positive migratory cells. Furthermore, transfection of SIP1 cDNA in MCF10A cells increased their vimentin expression both at the mRNA and protein levels and enhanced their migratory abilities in Boyden Chamber assays. Inversely, inhibition of SIP1 expression by RNAi strategies in BT-549 cells and MCF10A cells decreased vimentin expression. We also showed that SIP1 transfection did not activate the TOP-FLASH reporter system, suggesting that the beta-catenin/TCF pathway is not implicated in the regulation of vimentin by SIP1. Our results therefore implicate SIP1 in the regulation of vimentin observed in the EMT associated with breast tumor cell migration, a pathway that may contribute to the metastatic progression of breast cancer.