RACK1 promotes breast carcinoma migration/metastasis via activation of the RhoA/Rho kinase pathway
RACK1 promotes breast carcinoma migration/metastasis via activation of the RhoA/Rho kinase pathway
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RACK1通过激活RhoA/Rho激酶通路促进乳腺癌迁移/转移
DOI：
10.1007/s10549-010-0955-3
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发表时间：
2011-04-01
影响因子：
3.8
通讯作者：
Liu, Xiu-Ping
中科院分区：
文献类型：
--
作者：
Cao, Xi-Xi;Xu, Jing-Da;Liu, Xiu-Ping
我们的目的是获得RACK 1在乳腺癌迁移/转移中的作用的机制的理解。在乳腺癌细胞系中进行迁移测定。还应用靶向RACK 1的siRNA以及Rho激酶抑制剂。用免疫沉淀和免疫荧光法研究RACK 1/RhoA的相互作用。进行GTP-Rho下拉测定以评估RhoA的活化。我们还对160例乳腺癌标本进行了免疫组化。体外实验表明，RACK 1通过与RhoA相互作用并激活RhoA/Rho激酶途径来促进迁移。160例标本的免疫组化结果显示RACK 1与公认的肿瘤扩散指标和RhoA密切相关（均P < 0.05）。Kaplan-Meier生存分析显示RACK 1高表达与生存时间短相关（P < 0.001）。RACK 1是一种预后因子，通过与RhoA相互作用并激活RhoA/Rho激酶通路促进乳腺癌迁移/转移。
We aimed to gain a mechanistic understanding of the role of RACK1 in breast carcinoma migration/metastasis. Migration assays were conducted in breast carcinoma cell lines. siRNA targeting RACK1 as well as the Rho kinase inhibitor were also applied. Immunoprecipitation and immunofluorescence were used to study the RACK1/RhoA interaction. GTP-Rho pull-down assays were performed to assess the activation of RhoA. We also conducted immunohistochemistry in 160 breast carcinoma samples. Experiments in vitro showed that RACK1 promotes migration via interaction with RhoA and activation of the RhoA/Rho kinase pathway. Immunohistochemistry in 160 samples revealed that RACK1 is strongly correlated with accepted tumor spread indicators and RhoA (all P < 0.05). Kaplan-Meier survival analysis indicated a correlation between higher RACK1 expression and shorter survival times (P < 0.001). RACK1 is a prognostic factor that promotes breast carcinoma migration/metastasis by interacting with RhoA and activating the RhoA/Rho kinase pathway.