近日，美國生物化學雜志( Journal of Biological Chemistry)在線發(fā)表了中科院上海生科院營養(yǎng)所謝東研究組和生化與細胞所趙允研究組合作的研究論文,。揭示了接頭蛋白RACK1(Receptor of Activated Kinase1)在非小細胞肺癌中促進腫瘤發(fā)生發(fā)展的生物學功能以及Sonic Hedgehog信號通路在非小細胞肺癌中作用的新機制,。
謝東研究員指導的博士生石碩等發(fā)現(xiàn)在絕大多數(shù)的非小細胞肺癌中RACK1的表達顯著升高，并且它的表達水平與腫瘤的臨床和病理參數(shù)如腫瘤的分化,、分級和轉(zhuǎn)移有顯著的相關(guān)性,。在非小細胞肺癌中RACK1通過與Sonic hedgehog信號通路中的Smoothened結(jié)合，活化Smoothened,，從而激活Gli1的轉(zhuǎn)錄,，促進Sonic hedgehog 信號通路的激活。沉默RACK1可抑制Sonic hedgehog信號通路進而抑制非小細胞肺癌細胞生長和遷移以及體內(nèi)腫瘤的生長和轉(zhuǎn)移,。這些實驗結(jié)果表明RACK1有可能成為一個潛在的非小細胞肺癌治療靶點,。(生物谷Bioon.com)
doi:10.1074/jbc.M111.315416
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RACK1 promotes non-small-cell lung cancer tumorigenicity through activating sonic hedgehog signaling pathway
Shuo Shi1, Yue-Zhen Deng1, Jiang-Sha Zhao1, Xiao-Dan Ji1, Jun Shi2, Yu-Xiong Feng1, Guo Li1, Jing-Jing Li1, Di Zhu3, H. Phillip Koeffler4, Yun Zhao5 and Dong Xie1,
Non-small-cell lung cancer (NSCLC) is a deadly disease due to lack of effective diagnosis biomarker and therapeutic target. Much effort has been made in defining gene defects in NSCLC, but its full molecular pathogenesis remains unexplored. Here, we found RACK1 (Receptor of Activated Kinase 1) was elevated in most NSCLC, and its expression level correlated with key pathological characteristics including tumor differentiation, stage and metastasis. In addition, RACK1 activated sonic hedgehog signaling pathway by interacting with and activating Smoothened to mediate Gli1-dependent transcription in NSCLC cells. And silencing RACK1 dramatically inhibited in vivo tumor growth and metastasis by blocking the sonic hedgehog signaling pathway. These results suggest that RACK1 represents a new promising diagnosis biomarker and therapeutic target for NSCLC.
