Chen Meng, Sun Li-Xin, Yu Long, Liu Jun, Sun Li-Chao, Yang Zhi-Hua, Shu Xiong, Ran Yu-Liang
State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Beijing Research Institute of Orthopaedics and Traumatology, Beijing JiShuiTan Hospital, Beijing, China.
Cell Death Discov. 2021 Oct 11;7(1):282. doi: 10.1038/s41420-021-00681-z.
The fatality rate of non-small cell lung cancer (NSCLC) has been high due to the existence of cancer stem cells (CSCs). Non-muscle myosin heavy chain 9 (MYH9) can promote the progression of various tumors, but its effect on the stem cell-like characteristics of lung cancer cells (LCCs) has not been clarified. Our research found that the stemness characteristics of LCCs were significantly enhanced by the overexpression of MYH9, and the knockout of MYH9 had the opposite effects. The in vivo with inhibitor blebbistatin further confirmed the effect of MYH9 on the stem cell-like behavior of LCCs. Furthermore, western blotting showed that the expression level of CSCs markers (CD44, SOX2, Nanog, CD133, and OCT4) was also regulated by MYH9. Mechanistic studies have shown that MYH9 regulates stem cell-like features of LCCs by regulating the mTOR signaling pathway, which was supported by sphere formation experiments after LCCs were treated with inhibitors Rapamycin and CHIR-99021. Importantly, high expression of MYH9 in lung cancer is positively correlated with poor clinical prognosis and is an independent risk factor for patients with NSCLC.
由于癌症干细胞(CSCs)的存在,非小细胞肺癌(NSCLC)的死亡率一直很高。非肌肉肌球蛋白重链9(MYH9)可促进各种肿瘤的进展,但其对肺癌细胞(LCCs)干细胞样特性的影响尚未阐明。我们的研究发现,MYH9的过表达显著增强了LCCs的干性特征,而敲除MYH9则产生相反的效果。使用抑制剂blebbistatin进行的体内实验进一步证实了MYH9对LCCs干细胞样行为的影响。此外,蛋白质印迹法显示,CSCs标志物(CD44、SOX2、Nanog、CD133和OCT4)的表达水平也受MYH9调控。机制研究表明,MYH9通过调节mTOR信号通路来调控LCCs的干细胞样特征,这一结果在LCCs用抑制剂雷帕霉素和CHIR-99021处理后的成球实验中得到了支持。重要的是,肺癌中MYH9的高表达与不良临床预后呈正相关,并且是NSCLC患者的独立危险因素。