RACK1 promotes breast carcinoma migration/metastasis via activation of the RhoA/Rho kinase pathway

被引:43
作者
Cao, Xi-Xi [1 ]
Xu, Jing-Da [1 ]
Xu, Jia-Wen [1 ]
Liu, Xiao-Li [1 ]
Cheng, Yuan-Yuan [1 ]
Li, Qing-Quan [1 ]
Xu, Zu-De [1 ]
Liu, Xiu-Ping [1 ]
机构
[1] Fudan Univ, Dept Pathol, Shanghai Med Coll, Shanghai 200032, Peoples R China
关键词
RACK1; Breast carcinoma; Metastasis; Migration; RhoA/Rho kinase; ACTIN STRESS FIBERS; CANCER CELLS; RHO GTPASES; IN-VITRO; PROTEIN; INVASION; RECEPTOR; GROWTH; TRANSFORMATION; INVASIVENESS;
D O I
10.1007/s10549-010-0955-3
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:555 / 563
页数:9
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