Regulation of breast cancer cell motility by T-cell lymphoma invasion and metastasis-inducing protein.
Regulation of breast cancer cell motility by T-cell lymphoma invasion and metastasis-inducing protein.
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DOI：
10.1186/bcr2637
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Whitehead IP
中科院分区：
文献类型：
--
作者：
Adams HC 3rd;Chen R;Liu Z;Whitehead IP
T细胞淋巴瘤侵袭和转移诱导蛋白（Tiam 1）是一种Ras相关的C3肉毒杆菌毒素底物（Rac）特异性鸟嘌呤核苷酸交换因子，基于其诱导转移表型的能力而分离。在极化迁移的角质形成细胞中，Tiam 1位于前沿，在那里它与蛋白酶激活受体1（Par 1）复合物合作建立前后极性。尽管在包括乳腺癌在内的多种人类恶性肿瘤中观察到Tiam 1表达与肿瘤级别之间存在正相关性，但其在乳腺癌细胞中的作用尚未得到研究。Tiam 1表达和Rac活性在一组表现出不同程度的细胞运动性的人乳腺癌细胞系中进行了检查。Tiam 1对细胞运动性的贡献通过transwell运动性和伤口愈合测定直接检查。虽然我们在乳腺癌细胞系中观察到Tiam 1表达与细胞运动性之间存在显著的正相关性，但我们没有观察到Tiam 1表达与Rac活性总体水平之间存在相关性。与此一致，小干扰核糖核酸（siRNA）介导的Tiam 1表达抑制限制了Tiam 1表达高的细胞系（MDA-MB-231和MDA-MB-453）的运动性，但基本上不改变活化Rac的总体水平。Tiam 1过表达也不足以增加运动性更差的细胞（T-47 D）的运动性或增加Rac活性。免疫荧光和细胞分级表明Tiam 1主要存在于乳腺癌细胞的高尔基体中，在后一种情况下，Tiam 1与有限的Rac 1库共同破碎。与这种高尔基体定位一致，Tiam 1支持在使用MDA-MB-231和MDA-MB-435 S细胞的伤口愈合测定中响应于血清的细胞运动性和高尔基体重定向。Tiam 1表达与人乳腺癌细胞中的细胞运动性相关，并且是支持运动表型所必需的。本地化的内源性Tiam 1的高尔基体，其表现出的作用在高尔基体的重新定位，表明它可能支持运动通过一种机制，是离散的，从其已知的功能，在领先的动态。
T-cell lymphoma invasion and metastasis-inducing protein (Tiam1) is an Ras-related C3 botulinum toxin substrate (Rac)-specific guanine nucleotide exchange factor that was isolated based on its ability to induce a metastatic phenotype. In polarized migrating keratinocytes, Tiam1 is found at the leading edge, where it cooperates with the protease-activated receptor 1 (Par1) complex to establish front-to-rear polarity. Although a positive correlation has been observed between Tiam1 expression and tumor grade in a variety of human malignancies, including breast, its role in breast cancer cells has not yet been examined. Tiam1 expression and Rac activity were examined in a panel of human breast cancer cell lines that exhibit different degrees of cell motility. The contribution of Tiam1 to cell motility was directly examined by using transwell motility and wound-healing assays. Although we observed a striking, positive correlation between Tiam1 expression and cell motility in the panel of breast cancer cell lines, we did not observe a correlation between Tiam1 expression and overall levels of Rac activity. Consistent with this, small interfering ribonucleic acid (siRNA)-mediated suppression of Tiam1 expression limits the motility of cell lines in which Tiam1 expression is high (MDA-MB-231 and MDA-MB-453) but does not substantially alter the overall levels of activated Rac. Tiam1 overexpression is also not sufficient to increase the motility of more poorly motile cells (T-47D) or to increase Rac activity. Immunofluorescence and cellular fractionations indicate that Tiam1 is found predominantly in the Golgi of breast cancer cells, and in the latter case, Tiam1 was shown to co-fractionate with a limited pool of Rac1. Consistent with this Golgi localization, Tiam1 supports cell motility and Golgi reorientation in response to serum in a wound-healing assay using MDA-MB-231 and MDA-MB-435S cells. Tiam1 expression correlates with cell motility in human breast cancer cells and is required to support the motile phenotype. Localization of endogenous Tiam1 to the Golgi, and its demonstrated role in Golgi reorientation, suggest that it may support motility through a mechanism that is discrete from its known function in leading-edge dynamics.
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影响因子：
4.8
作者：
Buchsbaum, RJ;Connolly, BA;Feig, LA
通讯作者：
Feig, LA
影响因子：
8.8
作者：
通讯作者：
--
Tiam1在肝细胞癌中的过度表达预示着HCC患者的不良预后
影响因子：
6.4
作者：
Ding, Yi;Chen, Bin;Luo, Rongcheng
通讯作者：
Luo, Rongcheng
DOI：
10.1196/annals.1365.035
发表时间：
2006-01-01
期刊：
WOMEN'S HEALTH AND DISEASE: GYNECOLOGIC, ENDOCRINE, AND REPRODUCTIVE ISSUES
影响因子：
--
作者：
Hadjidakis, Dimitrios J.;Androulakis, Ioannis I.
通讯作者：
Androulakis, Ioannis I.
影响因子：
8
作者：
Korus, M;Mahon, GM;Whitehead, IP
通讯作者：
Whitehead, IP