Chai Shoujie, Xu Xia, Wang Yongfang, Zhou You, Zhang Chenchen, Yang Yiming, Yang Ying, Xu Haiyan, Xu Rongzhen, Wang Kai
Department of Respiratory Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of Hematology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Oncotarget. 2015 Jun 30;6(18):16069-83. doi: 10.18632/oncotarget.3866.
Highly tumorigenic stem-like cells, considered tumor-initiating cells (TICs), are the main cause of lung cancer initiation, relapse, and drug resistance. In this study, we identified that Ca2+/calmodulin-dependent protein kinase IIγ (CaMKIIγ) was aberrantly expressed in highly tumorigenic stem-like lung cancer cells, and was also correlated with poor prognosis in human lung cancer. Functionally, CaMKIIγ enhanced stem-like traits and the tumorigenicity of lung cancer cells in an Akt- and β-catenin-dependent manner. In addition, we found that CaMKIIγ upregulated Oct4 expression via Akt-mediated histone acetylation. Taken together, our findings reveal a critical role of CaMKIIγ in regulating the stemness and tumorigenicity of lung cancer cells and offer a promising therapeutic target for TICs.
具有高度致瘤性的干细胞样细胞，被认为是肿瘤起始细胞（TICs），是肺癌发生、复发和耐药的主要原因。在本研究中，我们发现Ca2+/钙调蛋白依赖性蛋白激酶IIγ（CaMKIIγ）在具有高度致瘤性的肺癌干细胞样细胞中异常表达，并且与人类肺癌的不良预后相关。在功能上，CaMKIIγ以Akt和β-连环蛋白依赖性方式增强肺癌细胞的干细胞样特性和致瘤性。此外，我们发现CaMKIIγ通过Akt介导的组蛋白乙酰化上调Oct4表达。综上所述，我们的研究结果揭示了CaMKIIγ在调节肺癌细胞干性和致瘤性中的关键作用，并为TICs提供了一个有前景的治疗靶点。
