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Ribosomal RACK1 promotes chemoresistance and growth in human hepatocellular carcinoma
Yuanyuan Ruan, … , Aiguo Shen, Jianxin Gu
Yuanyuan Ruan, … , Aiguo Shen, Jianxin Gu
Published June 1, 2012
Citation Information: J Clin Invest. 2012;122(7):2554-2566. https://doi.org/10.1172/JCI58488.
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Research Article Oncology

Ribosomal RACK1 promotes chemoresistance and growth in human hepatocellular carcinoma

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Abstract

Coordinated translation initiation is coupled with cell cycle progression and cell growth, whereas excessive ribosome biogenesis and translation initiation often lead to tumor transformation and survival. Hepatocellular carcinoma (HCC) is among the most common and aggressive cancers worldwide and generally displays inherently high resistance to chemotherapeutic drugs. We found that RACK1, the receptor for activated C-kinase 1, was highly expressed in normal liver and frequently upregulated in HCC. Aberrant expression of RACK1 contributed to in vitro chemoresistance as well as in vivo tumor growth of HCC. These effects depended on ribosome localization of RACK1. Ribosomal RACK1 coupled with PKCβII to promote the phosphorylation of eukaryotic initiation factor 4E (eIF4E), which led to preferential translation of the potent factors involved in growth and survival. Inhibition of PKCβII or depletion of eIF4E abolished RACK1-mediated chemotherapy resistance of HCC in vitro. Our results imply that RACK1 may function as an internal factor involved in the growth and survival of HCC and suggest that targeting RACK1 may be an efficacious strategy for HCC treatment.

Authors

Yuanyuan Ruan, Linlin Sun, Yuqing Hao, Lijing Wang, Jiejie Xu, Wen Zhang, Jianhui Xie, Liang Guo, Lei Zhou, Xiaojing Yun, Hongguang Zhu, Aiguo Shen, Jianxin Gu

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Figure 1

RACK1 is preferentially expressed in normal liver and frequently upregulated in HCC.

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RACK1 is preferentially expressed in normal liver and frequently upregul...
(A) Assessment of RACK1 transcripts in a variety of normal human tissues. Total RNA was extracted from frozen fresh normal tissues, and quantitative real-time PCR was performed to assess RACK1 transcripts, with β-actin mRNA as the internal control. Numbers listed are mean of each group. (B) Expression of RACK1 in an immortalized liver cell line and HCC cell lines. (C) Expression of RACK1 in paired liver tissue samples. N, adjacent nontumor sections; T, tumor sections. (D) MRNA levels of RACK1 in paired liver tissue samples. Total RNA was extracted from paired liver tissue samples, and RACK1 mRNA levels were detected by quantitative real-time PCR, with β-actin as internal control. (E) Expression of RACK1 in HCC samples at different stages. RACK1 expression was detected by immunohistochemistry in 162 HCC samples. In B and C, numbers represent relative expression of RACK1, which was quantified by comparing it with GAPDH. Original magnification, ×400; scale bars: 20 μm.

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