論文 - 詳細
| RRC ID | 36003 |
|---|---|
| 著者 | Chen CL, Uthaya Kumar DB, Punj V, Xu J, Sher L, Tahara SM, Hess S, Machida K. |
| タイトル | NANOG Metabolically Reprograms Tumor-Initiating Stem-like Cells through Tumorigenic Changes in Oxidative Phosphorylation and Fatty Acid Metabolism. |
| ジャーナル | Cell Metab |
| Abstract |
Stem cell markers, including NANOG, have been implicated in various cancers; however, the functional contribution of NANOG to cancer pathogenesis has remained unclear. Here, we show that NANOG is induced by Toll-like receptor 4 (TLR4) signaling via phosphorylation of E2F1 and that downregulation of Nanog slows down hepatocellular carcinoma (HCC) progression induced by alcohol western diet and hepatitis C virus protein in mice. NANOG ChIP-seq analyses reveal that NANOG regulates the expression of genes involved in mitochondrial metabolic pathways required to maintain tumor-initiating stem-like cells (TICs). NANOG represses mitochondrial oxidative phosphorylation (OXPHOS) genes, as well as ROS generation, and activates fatty acid oxidation (FAO) to support TIC self-renewal and drug resistance. Restoration of OXPHOS activity and inhibition of FAO renders TICs susceptible to a standard care chemotherapy drug for HCC, sorafenib. This study provides insights into the mechanisms of NANOG-mediated generation of TICs, tumorigenesis, and chemoresistance through reprogramming of mitochondrial metabolism. |
| 巻・号 | 23(1) |
| ページ | 206-19 |
| 公開日 | 2016-1-12 |
| DOI | 10.1016/j.cmet.2015.12.004 |
| PII | S1550-4131(15)00619-1 |
| PMID | 26724859 |
| PMC | PMC4715587 |
| MeSH | Animals Carcinogenesis / metabolism* Carcinogenesis / pathology Carcinoma, Hepatocellular / metabolism* Carcinoma, Hepatocellular / pathology Cell Line, Tumor Cell Self Renewal Drug Resistance, Neoplasm E2F1 Transcription Factor / metabolism Fatty Acids Gene Expression Regulation, Neoplastic HEK293 Cells Homeodomain Proteins / physiology* Humans Lipid Metabolism Liver Neoplasms, Experimental / metabolism* Liver Neoplasms, Experimental / pathology Mitochondria, Liver / metabolism Nanog Homeobox Protein Neoplastic Stem Cells / metabolism* Oxidation-Reduction Oxidative Phosphorylation Oxidative Stress Phosphorylation Protein Processing, Post-Translational Reactive Oxygen Species / metabolism Transcriptional Activation |
| IF | 21.567 |
| 引用数 | 110 |
| WOS 分野 | ENDOCRINOLOGY & METABOLISM CELL BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | News |
| 各媒体での言及数の合計 | 26 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC04878 |