IBP regulates epithelial-to-mesenchymal transition and the motility of breast cancer cells via Rac1, RhoA and Cdc42 signaling pathways.
IBP regulates epithelial-to-mesenchymal transition and the motility of breast cancer cells via Rac1, RhoA and Cdc42 signaling pathways.
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IBP 通过 Rac1、RhoA 和 Cdc42 信号通路调节上皮间质转化和乳腺癌细胞的运动。
作者：
上皮间质转化（EMT）是上皮性肿瘤侵袭和转移的关键过程。然而，这种转变背后的分子机制知之甚少。在这项研究中，我们证明，干扰素调节因子4结合蛋白（IBP）调节EMT和乳腺癌细胞的运动通过Rac 1，RhoA和Cdc 42信号通路。我们发现IBP表达的增加与乳腺癌的进展有关，并且在匹配的远处转移中IBP蛋白水平显著升高。高IBP水平还预测乳腺癌患者的总生存期较短。此外，在乳腺癌细胞中，IBP的强制表达降低了上皮标志物E-cadherin的表达，但增加了间质标志物的表达。相反，在转移性乳腺肿瘤细胞中沉默IBP促进了上皮形态的转变，伴随着E-钙粘蛋白表达的增加和间充质标志物表达的减少。IBP沉默也降低了EMT诱导转录因子（Snail、Slug、ZEB 1和ZEB 2）的表达。此外，我们确定了在乳腺癌细胞中，IBP在表皮生长因子（EGF）诱导的内源性EMT中的作用和IBP减弱EGF受体（EGFR）信号传导的缺失。此外，IBP调节乳腺癌细胞的迁移、侵袭和基质金属蛋白酶的产生，以及肌动蛋白细胞骨架重排和GTP-Rac 1、GTP-RhoA和GTP-Cdc 42的激活。综上所述，我们的研究结果证明了IBP在促进乳腺癌细胞转移潜能方面的致癌特性。
Epithelial-to-mesenchymal transition (EMT) is a crucial process for the invasion and metastasis of epithelial tumors. However, the molecular mechanisms underlying this transition are poorly understood. In this study, we demonstrate that interferon regulatory factor 4 binding protein (IBP) regulates EMT and the motility of breast cancer cells through Rac1, RhoA and Cdc42 signaling pathways. We found that increased expression of IBP was associated with the progression of breast cancer and that IBP protein levels were significantly elevated in matched distant metastases. High IBP levels also predict shorter overall survival of breast cancer patients. Furthermore, the forced expression of IBP decreased the expression of the epithelial marker E-cadherin but increased the mesenchymal markers in breast cancer cells. In contrast, silencing IBP in metastatic breast tumor cells promoted a shift toward an epithelial morphology concomitant with increased expression of E-cadherin and decreased expression of mesenchymal markers. IBP silencing also reduced the expression of EMT-inducing transcription factors (Snail, Slug, ZEB1 and ZEB2). Moreover, we identified a role for IBP in endogenous EMT induced by epidermal growth factor (EGF) and deletion of IBP attenuated EGF receptor (EGFR) signaling in breast cancer cells. Furthermore, IBP regulates the migration, invasion and matrix metalloprotease production in breast cancer cells as well as actin cytoskeleton rearrangement and the activation of GTP-Rac1, GTP-RhoA and GTP-Cdc42. Taken together, our findings demonstrate an oncogenic property for IBP in promoting the metastatic potential of breast cancer cells.
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影响因子：
15.9
作者：
Becart, Stephane;Charvet, Celine;Altman, Amnon
通讯作者：
Altman, Amnon
DOI：
10.4049/jimmunol.0902573
发表时间：
2009-12-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Canonigo-Balancio AJ;Fos C;Prod'homme T;Bécart S;Altman A
通讯作者：
Altman A
影响因子：
2.5
作者：
Hardy, Katharine M.;Booth, Brian W.;Hendrix, Mary J. C.;Salomon, David S.;Strizzi, Luigi
通讯作者：
Strizzi, Luigi
影响因子：
4.8
作者：
Hey, Fiona;Czyzewicz, Nathan;Sablitzky, Fred
通讯作者：
Sablitzky, Fred
影响因子：
6.5
作者：
Hotfilder, M;Baxendale, S;Sablitzky, F
通讯作者：
Sablitzky, F