Abstract
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.
Highlights
Lung cancer has always been considered a serious disease characterized by poor prognosis and a low survival rate
The occurrence and maintenance of lung cancer depend on the presence of lung cancer stem cells (LCSCs), which contribute to the poor prognosis of patients with lung cancer [3,4,5,6]
The high morbidity, high mortality, and low survival rate of patients with non-small cell lung cancer (NSCLC) are closely related to CSCs, which have the biological characteristics of unlimited self-renewal, high tumorigenicity, high invasion, and migration, and strong drug resistance [35,36,37,38]
Summary
Lung cancer has always been considered a serious disease characterized by poor prognosis and a low survival rate. Researchers found CD133, CD44, and other LCSC surface markers and related signal pathways [9,10,11,12,13], further confirming the existence of LCSCs. At present, various targeted drugs for cancer stem cells (CSCs) have entered phase I or phase II clinical trials [14,15,16], which is expected to bring a breakthrough in cancer therapy. We used an immunohistochemical (IHC) assay to analyze the expression of MYH9 in clinical tissue samples of lung cancer and found that it can be used as an independent factor in evaluating the prognosis of patients with NSCLC
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