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The Nα-acetyl-L-lysine/Loxl2/H2O2 promotes intestinal tumor growth in Drosophila and cell proliferation in human colorectal cancer

Published:26 August 2025 DOI: 10.1016/j.celrep.2025.116126 PMID: 40811058
Lei Geng,?Zhen Fan,?Rongbing Chen,?Kyu-Chan Cho,?Yining Liu,?Yu Cheng,?Jingfeng Yang,?Ying Zhang,?Xuefei Wei,?Liyuan Gong,?Yingyu Tang,?Zhan Xu,?Wuren Huang,?Shahzad Toufeeq,?Zongzhao Zhai,?Lei Pan,?Jun Zhang,?Bin Li,?Brenda T Beerntsen,?Ji-Hoon Lee,?Youli Xiao,?Younghwa Na,?Won-Jae Lee,?Erjun Ling

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.

Substances (24)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Erythromycin 114-07-8 C37H67NO13 944 suppliers $5.00-$2245.70
Erythromycin 114-07-8 C37H67NO13 944 suppliers $5.00-$2245.70
Erythromycin 114-07-8 C37H67NO13 944 suppliers $5.00-$2245.70
Erythromycin 114-07-8 C37H67NO13 944 suppliers $5.00-$2245.70
3-Amino-1,2,4-Triazole 61-82-5 C2H4N4 602 suppliers $7.62-$4864.00
3-Amino-1,2,4-Triazole 61-82-5 C2H4N4 602 suppliers $7.62-$4864.00
3-Amino-1,2,4-Triazole 61-82-5 C2H4N4 602 suppliers $7.62-$4864.00
3-Amino-1,2,4-Triazole 61-82-5 C2H4N4 602 suppliers $7.62-$4864.00
Bleomycin sulfate 9041-93-4 C110H168N34O46S7 555 suppliers $28.00-$4290.00
Bleomycin sulfate 9041-93-4 C110H168N34O46S7 555 suppliers $28.00-$4290.00

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