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.
Keywords:
CaMKIIγ; lung cancer; stem-like; tumorigenicity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis
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Blotting, Western
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Calcium-Calmodulin-Dependent Protein Kinase Type 2 / genetics
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Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism*
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Cell Proliferation*
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Cell Transformation, Neoplastic / metabolism
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Cell Transformation, Neoplastic / pathology*
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Chromatin Immunoprecipitation
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Flow Cytometry
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Humans
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Immunoenzyme Techniques
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Lung Neoplasms / metabolism
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Lung Neoplasms / pathology*
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Mice
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Mice, Inbred BALB C
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Mice, Inbred NOD
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Mice, Nude
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Mice, SCID
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Neoplastic Stem Cells / metabolism
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Neoplastic Stem Cells / pathology*
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Prognosis
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RNA, Messenger / genetics
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Real-Time Polymerase Chain Reaction
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction
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Tumor Cells, Cultured
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Xenograft Model Antitumor Assays
Substances
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RNA, Messenger
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Calcium-Calmodulin-Dependent Protein Kinase Type 2