論文 - 詳細
| RRC ID | 85584 |
|---|---|
| 著者 | Geng L, Fan Z, Chen R, Cho KC, Liu Y, Cheng Y, Yang J, Zhang Y, Wei X, Gong L, Tang Y, Xu Z, Huang W, Toufeeq S, Zhai Z, Pan L, Zhang J, Li B, Beerntsen BT, Lee JH, Xiao Y, Na Y, Lee WJ, Ling E. |
| タイトル | The Nα-acetyl-L-lysine/Loxl2/H2O2 promotes intestinal tumor growth in Drosophila and cell proliferation in human colorectal cancer. |
| ジャーナル | Cell Rep |
| Abstract |
A cancer-associated microbiome is considered a carcinogen capable of affecting tumor initiation and/or progression. However, little is known about the molecular mechanisms of tumor-microbiome interactions. Here, we show that Staphylococcus sciuri promotes Drosophila intestinal tumor growth by inducing intestinal stem cell (ISC) division. Metabolomic analysis revealed that Nα-acetyl-L-lysine derived from S. sciuri, but not other naturally Nα-acetylated L-type amino acids, promotes ISC division in germ-free and conventional animals. Biochemical analysis further shows that GCN5-related N-acetyl transferases of S. sciuri catalyze L-lysine and acetyl-CoA into Nα-acetyl-L-lysine. Drosophila lysyl oxidase-like 2 enzyme subsequently catalyzes Nα-acetyl-L-lysine to produce H2O2, forming the Nα-acetyl-L-lysine/Loxl2/H2O2 axis that activates ATR-Chk1 and JNK and subsequently triggers the JAK/STAT pathway required for ISC division and tumor growth. The Nα-acetyl-L-lysine/Loxl2/H2O2 axis also regulates human colorectal cancer cell division. The identification of Nα-acetyl-L-lysine/Loxl2/H2O2 axis provides distinct insights into the complex interplay among microbiome, tumor, and oxidative stress. |
| 巻・号 | 44(8) |
| ページ | 116126 |
| 公開日 | 2025-8-12 |
| DOI | 10.1016/j.celrep.2025.116126 |
| PII | S2211-1247(25)00897-6 |
| PMID | 40811058 |
| MeSH | Animals Cell Proliferation Colorectal Neoplasms* / metabolism Colorectal Neoplasms* / pathology Drosophila Proteins* / metabolism Drosophila melanogaster* / metabolism Drosophila melanogaster* / microbiology Humans Hydrogen Peroxide* / metabolism Intestinal Neoplasms* / metabolism Intestinal Neoplasms* / pathology Lysine* / analogs & derivatives Lysine* / metabolism Signal Transduction |
| IF | 8.109 |
| 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 | Bluesky |
| 各媒体での言及数の合計 | 5 |
| 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 | |
| ショウジョウバエ | 5680R-2 M2L-2957 DGRC#109029 |