RACK1 promotes breast carcinoma proliferation and invasion/metastasis in vitro and in vivo.
A yeast two-hybrid system was utilized to identify novel PI3K p110alpha-interacting proteins, of which receptor of activated protein kinase C1 (RACK1) was chosen for successive detailed analyses. Our aim was to investigate the function(s) of RACK1 and its involvement in mechanisms of breast carcinoma proliferation and invasion/metastasis. Experiments in breast carcinoma cell lines stably transfected with RACK1, as well as nude mouse models, showed that RACK1 promotes breast carcinoma proliferation and invasion/metastasis in vitro and in vivo. Conversely, knockdown of RACK1 by siRNA in vitro inhibited proliferation, migration, and invasion. In cell lines stably transfected with RACK1, p-AKT, cyclin D1, cyclin D3, and CD147 expression, as well as MMP2 activity, were elevated. RACK1-induced migration could be inhibited by the addition of Rho-kinase inhibitor. In 160 breast carcinoma cases, survival analyses established that RACK1 is an independent prognostic factor for poor outcome (P < 0.001). In conclusion, RACK1 is an independent prognosis-related factor and promotes breast carcinoma proliferation and invasion/metastasis in vitro and in vivo.
Cao
Xi-Xi
XX
Department of Pathology, Shanghai Medical College, Fudan University, 138 Yi Xue Yuan Road, Shanghai, 200032, China.
Xu
Jing-Da
JD
Xu
Jia-Wen
JW
Liu
Xiao-Li
XL
Cheng
Yuan-Yuan
YY
Wang
Wen-Juan
WJ
Li
Qing-Quan
QQ
Chen
Qi
Q
Xu
Zu-De
ZD
Liu
Xiu-Ping
XP
D000328:Adult; D000368:Aged; D000818:Animals; D051926:Basigin / Q000378:metabolism; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D002277:Carcinoma / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D058534:Class I Phosphatidylinositol 3-Kinases; D019938:Cyclin D1 / Q000378:metabolism; D056743:Cyclin D3 / Q000378:metabolism; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009367:Neoplasm Staging; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011379:Prognosis; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D020798:Two-Hybrid System Techniques; D023041:Xenograft Model Antitumor Assays; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
C497886:BSG protein, human; C530104:CCND1 protein, human; C534696:CCND3 protein, human; D056743:Cyclin D3; D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; C419368:RACK1 protein, human; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D019938:Cyclin D1; D051926:Basigin; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D051057:Proto-Oncogene Proteins c-akt; D054460:rho-Associated Kinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D019204:GTP-Binding Proteins