近日,，由上海復(fù)旦大學(xué)顧建新教授所在的研究組發(fā)現(xiàn)，核糖體蛋白RACK1能夠促進(jìn)了肝細(xì)胞癌（HCC）的生長及化療耐藥,。相關(guān)研究成果于6月1日發(fā)表在The Journal of Clinical Investigation上,。
眾所周知，翻譯的起始與細(xì)胞周期進(jìn)程及細(xì)胞生長相偶聯(lián),，然而,，過多的核糖體的合成及翻譯起始通常都導(dǎo)致了腫瘤的轉(zhuǎn)化及存活。
肝細(xì)胞癌(HCC)是世界上最常見的惡性癌癥之一,，對化療藥物通常都表現(xiàn)出高的耐受性,。RACK1是激活的蛋白激酶C1的受體。在這項(xiàng)研究里,，研究人員發(fā)現(xiàn)RACK1在正常肝臟中高表達(dá),，并在肝細(xì)胞癌中頻繁的被上調(diào)。他們發(fā)現(xiàn),，RACK1的異常表達(dá)促進(jìn)了肝細(xì)胞癌的化療抗性及生長,，而這些作用主要依賴于RACK1的核糖體定位。
進(jìn)一步研究發(fā)現(xiàn),，核糖體RACK1通過偶聯(lián)PKCβII促進(jìn)了真核起始因子4E(eIF4E)的磷酸化,，導(dǎo)致了與生長及生存有關(guān)的蛋白因子的優(yōu)先翻譯。而抑制PKCβII或者是消耗eIF4E則破壞了由RACK1介導(dǎo)的肝細(xì)胞癌的化療抗性,。
總的來說,，該研究表明了RACK1很可能是與肝細(xì)胞癌的生長及存活有關(guān)的內(nèi)源性因子。為此,，研究人員表示,，靶向RACK1很可能會成為一種有效的的策略來治療肝細(xì)胞癌,。（生物谷Deepblue編譯）
doi: 10.1172/JCI58488
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Ribosomal RACK1 promotes chemoresistance and growth in human hepatocellular carcinoma
Yuanyuan Ruan, Linlin Sun, Yuqing Hao, Lijing Wang, Jiejie Xu, Wen Zhang, Jianhui Xie, Liang Guo, Lei Zhou, Xiaojing Yun, Hongguang Zhu, Aiguo Shen and Jianxin Gu.
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.
