RACK1 Promotes Non-small-cell Lung Cancer Tumorigenicity through Activating Sonic Hedgehog Signaling Pathway
RACK1 Promotes Non-small-cell Lung Cancer Tumorigenicity through Activating Sonic Hedgehog Signaling Pathway
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RACK1通过激活Sonic Hedgehog信号通路促进非小细胞肺癌致瘤性
DOI：
10.1074/jbc.m111.315416
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发表时间：
2012-03-09
影响因子：
4.8
通讯作者：
Xie, Dong
中科院分区：
文献类型：
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作者：
Shi, Shuo;Deng, Yue-Zhen;Xie, Dong
非小细胞肺癌（non-small cell lung cancer，NSCLC）是一种缺乏有效诊断标志物和治疗靶点的致死性疾病。在非小细胞肺癌基因缺陷的定义方面已经做了很多努力，但其完整的分子发病机制尚未探索。我们发现RACK 1（receptor of activated kinase 1，活化激酶1受体）在大多数NSCLC中表达升高，其表达水平与肿瘤分化、分期、转移等关键病理特征相关。此外，RACK 1通过与Smoothened相互作用并激活Smoothened来激活Sonic Hedgehog信号通路，从而介导NSCLC细胞中Gli 1依赖性转录。沉默RACK 1通过阻断音刺猬信号通路显著抑制体内肿瘤生长和转移。这些结果表明，RACK 1代表了一个新的有前途的诊断生物标志物和治疗靶点的NSCLC。
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.