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RACK1 promotes breast carcinoma proliferation and invasion/metastasis in vitro and in vivo

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Abstract

A yeast two-hybrid system was utilized to identify novel PI3K p110α-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.

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Acknowledgment

This study was supported by National Nature Science Foundation of China (Nos. 30870972 and 30872971).

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Authors and Affiliations

  1. Department of Pathology, Shanghai Medical College, Fudan University, 138 Yi Xue Yuan Road, Shanghai, 200032, China

    Xi-Xi Cao, Jing-Da Xu, Jia-Wen Xu, Xiao-Li Liu, Yuan-Yuan Cheng, Wen-Juan Wang, Qing-Quan Li, Qi Chen, Zu-De Xu & Xiu-Ping Liu

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  1. Xi-Xi Cao
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Correspondence to Xiu-Ping Liu.

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Cao, XX., Xu, JD., Xu, JW. et al. RACK1 promotes breast carcinoma proliferation and invasion/metastasis in vitro and in vivo. Breast Cancer Res Treat 123, 375–386 (2010). https://doi.org/10.1007/s10549-009-0657-x

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