RACK1 promotes breast carcinoma migration/metastasis via activation of the RhoA/Rho kinase pathway.
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.
Cao
Xi-Xi
XX
Department of Pathology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Xu
Jing-Da
JD
Xu
Jia-Wen
JW
Liu
Xiao-Li
XL
Cheng
Yuan-Yuan
YY
Li
Qing-Quan
QQ
Xu
Zu-De
ZD
Liu
Xiu-Ping
XP
D001943:Breast Neoplasms / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D004789:Enzyme Activation; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008856:Microscopy, Fluorescence / Q000379:methods; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism*; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000378:metabolism*; D016896:Treatment Outcome; D054460:rho-Associated Kinases / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D009363:Neoplasm Proteins; C419368:RACK1 protein, human; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; C066737:RHOA protein, human; D054460:rho-Associated Kinases; D019204:GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein