近日，美国生物化学杂志( Journal of Biological Chemistry)在线发表了中科院上海生科院营养所谢东研究组和生化与细胞所赵允研究组合作的研究论文。揭示了接头蛋白RACK1(Receptor of Activated Kinase1)在非小细胞肺癌中促进肿瘤发生发展的生物学功能以及Sonic Hedgehog信号通路在非小细胞肺癌中作用的新机制。
谢东研究员指导的博士生石硕等发现在绝大多数的非小细胞肺癌中RACK1的表达显著升高，并且它的表达水平与肿瘤的临床和病理参数如肿瘤的分化、分级和转移有显著的相关性。在非小细胞肺癌中RACK1通过与Sonic hedgehog信号通路中的Smoothened结合，活化Smoothened，从而激活Gli1的转录，促进Sonic hedgehog 信号通路的激活。沉默RACK1可抑制Sonic hedgehog信号通路进而抑制非小细胞肺癌细胞生长和迁移以及体内肿瘤的生长和转移。这些实验结果表明RACK1有可能成为一个潜在的非小细胞肺癌治疗靶点。(生物谷Bioon.com)
doi:10.1074/jbc.M111.315416
PMC:
PMID:
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.
