論文 - 詳細
| RRC ID | 70440 |
|---|---|
| 著者 | Haraoka Y, Akieda Y, Nagai Y, Mogi C, Ishitani T. |
| タイトル | Zebrafish imaging reveals TP53 mutation switching oncogene-induced senescence from suppressor to driver in primary tumorigenesis. |
| ジャーナル | Nat Commun |
| Abstract |
Most tumours are thought to arise through oncogenic cell generation followed by additional mutations. How a new oncogenic cell primes tumorigenesis by acquiring additional mutations remains unclear. We show that an additional TP53 mutation stimulates primary tumorigenesis by switching oncogene-induced senescence from a tumour suppressor to a driver. Zebrafish imaging reveals that a newly emerged oncogenic cell with the RasG12V mutation becomes senescent and is eliminated from the epithelia, which is prevented by adding a TP53 gain-of-function mutation (TP53R175H) into RasG12V cells. Surviving RasG12V-TP53R175H double-mutant cells senesce and secrete senescence-associated secretory phenotype (SASP)-related inflammatory molecules that convert neighbouring normal cells into SASP factor-secreting senescent cells, generating a heterogeneous tumour-like cell mass. We identify oncogenic cell behaviours that may control the initial human tumorigenesis step. Ras and TP53 mutations and cellular senescence are frequently detected in human tumours; similar switching may occur during the initial step of human tumorigenesis. |
| 巻・号 | 13(1) |
| ページ | 1417 |
| 公開日 | 2022-3-18 |
| DOI | 10.1038/s41467-022-29061-6 |
| PII | 10.1038/s41467-022-29061-6 |
| PMID | 35304872 |
| PMC | PMC8933407 |
| MeSH | Animals Carcinogenesis / genetics Cellular Senescence* / genetics Mutation Oncogenes / genetics Tumor Suppressor Protein p53 / genetics* Zebrafish* / genetics |
| IF | 12.121 |
| 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 | 15 |
| 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 | |
| ゼブラフィッシュ | Tg(krt4p:gal4; UAS:EGFP) |