title: Ca2+/calmodulin-dependent protein kinase IIγ enhances stem-like traits and tumorigenicity of lung cancer cells.
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 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.
authors.affiliation: Department of Respiratory Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Shoujie
authors.initials: S
authors.lastname: Chai
authors.affiliation: Department of Respiratory Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Respiratory Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Yongfang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Respiratory Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: You
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Respiratory Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Chenchen
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Respiratory Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Respiratory Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Hematology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Rongzhen
authors.initials: R
authors.lastname: Xu
authors.affiliation: Department of Respiratory Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology*; D047369:Chromatin Immunoprecipitation; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D008819:Mice, Nude; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D012333:RNA, Messenger; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2
keywords: CaMKIIγ; lung cancer; stem-like; tumorigenicity