Guo Tao, Kong Jing, Liu Yang, Li Zhuoshi, Xia Jianglong, Zhang Yan, Zhao Shilei, Li Fengzhou, Li Jinxiu, Gu Chundong
Department of Thoracic Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China; Lung Cancer Diagnosis and Treatment Center of Dalian, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China.
College of Stomatology, Dalian Medical University, Dalian, 116044, China.
Biochem Biophys Res Commun. 2017 May 20;487(1):153-159. doi: 10.1016/j.bbrc.2017.04.033. Epub 2017 Apr 8.
Aberrant overexpression of the transcription/translation factor Y-box-binding protein-1 (YBX1) is associated with non-small cell lung cancer (NSCLC) aggressiveness. Cancer stem cells (CSCs) contribute to the tumorigenesis and metastasis of NSCLC. Hitherto, the mechanism by which YBX1 regulates CSCs and metastasis in NSCLC remains unclear. Here, we demonstrated that YBX1 levels were elevated in NSCLC tissues and cell lines. Enforced expression of YBX1 promoted NSCLC cells invasion, sphere forming ability and ALDH1 population. Conversely, reduced YBX1 impaired CSC properties of NSCLC cells in vitro and tumor-initiating frequencies, as well as metastasis in vivo. Importantly, we described a mechanism whereby YBX1 directly promoted NANOG, a transcription factor, transcriptional activation. Depletion of NANOG abolished the enhanced ability of invasion and sphere formation in YBX1 elevated-A549 cells. Collectively, these findings demonstrate a novel role of YBX1 in maintaining the stemness of CSCs and metastasis, unveiling YBX1 as promising therapeutic target for NSCLC treatments.
转录/翻译因子Y盒结合蛋白1（YBX1）的异常过表达与非小细胞肺癌（NSCLC）的侵袭性相关。癌症干细胞（CSCs）促成了NSCLC的肿瘤发生和转移。迄今为止，YBX1调节NSCLC中CSCs和转移的机制仍不清楚。在此，我们证明YBX1水平在NSCLC组织和细胞系中升高。YBX1的强制表达促进了NSCLC细胞的侵袭、成球能力和醛脱氢酶1（ALDH1）群体。相反，YBX1的减少损害了NSCLC细胞在体外的CSC特性和肿瘤起始频率，以及在体内的转移。重要的是，我们描述了一种机制，通过该机制YBX1直接促进转录因子NANOG的转录激活。NANOG的缺失消除了YBX1升高的A549细胞中增强的侵袭和成球能力。总的来说，这些发现证明了YBX1在维持CSCs干性和转移方面的新作用，揭示YBX1作为NSCLC治疗有前景的治疗靶点。
