論文 - 詳細
| RRC ID | 36312 |
|---|---|
| 著者 | Nakamura M, Ohsawa S, Igaki T. |
| タイトル | Mitochondrial defects trigger proliferation of neighbouring cells via a senescence-associated secretory phenotype in Drosophila. |
| ジャーナル | Nat Commun |
| Abstract |
Cell-cell interactions play important roles in epithelial tumorigenesis. Here we show in Drosophila imaginal epithelium that Ras activation and mitochondrial dysfunction, frequent alterations in cancers, cause cellular senescence and senescence-associated secretory phenotype (SASP), which leads to overgrowth of neighbouring tissue. Ras-activated cells express several hallmarks of cellular senescence such as elevation of senescence-associated β-galactosidase activity, upregulation of the Cdk inhibitor Dacapo, heterochromatinization and cellular hypertrophy. Strikingly, defects in mitochondrial function cause Ras-activated cells to undergo DNA damage response, cell cycle arrest and thereby induce SASP, exhibiting full aspects of cellular senescence. Mechanistically, mitochondrial defects in conjunction with Ras cause production of reactive oxygen species, downregulation of CycE activity and activation of p53, which cooperate together to trigger a cell cycle arrest-Jun N-terminal kinase (JNK) feedback loop that amplifies JNK activation, leading to upregulation of the inflammatory cytokine Unpaired. Our data suggest that mitochondrial defects promote Ras-induced cellular senescence and thereby contribute to tumour progression through SASP. |
| 巻・号 | 5 |
| ページ | 5264 |
| 公開日 | 2014-10-27 |
| DOI | 10.1038/ncomms6264 |
| PII | ncomms6264 |
| 解説 | the National Institute of Genetics Stock Center and the Drosophila Genetic Resource Center for fly stocks. |
| PMID | 25345385 |
| MeSH | Animals Biomarkers / metabolism Cell Proliferation Cellular Senescence* Drosophila Proteins / metabolism* Drosophila melanogaster / cytology* Drosophila melanogaster / metabolism* Enzyme Activation Eye / metabolism G1 Phase Cell Cycle Checkpoints Green Fluorescent Proteins / metabolism Hypertrophy JNK Mitogen-Activated Protein Kinases / metabolism MAP Kinase Signaling System Mitochondria / metabolism* Models, Biological Phenotype Tumor Suppressor Protein p53 / metabolism ras Proteins / metabolism |
| IF | 12.121 |
| 引用数 | 33 |
| WOS 分野 | 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 | X(Twitter) |
| 各媒体での言及数の合計 | 12 |
| 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 | |
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