Ca2+/calmodulin-dependent protein kinase IIγ enhances stem-like traits and tumorigenicity of lung cancer cells

// Shoujie Chai 1,* , Xia Xu 1,* , Yongfang Wang 1 , You Zhou 1 , Chenchen Zhang 1 , Yiming Yang 1 , Ying Yang 1 , Haiyan Xu 1 , Rongzhen Xu 2 and Kai Wang 1 1 Department of Respiratory Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China 2 Department of Hematology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China * These authors have contributed equally to this work Correspondence to: Kai Wang, email: // Keywords : CaMKIIγ, stem-like, tumorigenicity, lung cancer Received : February 10, 2015 Accepted : March 31, 2015 Published : April 19, 2015 Abstract 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 Ca 2+ /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.