格式化
酶
化学
癌细胞
醛脱氢酶
蛋氨酸
生物化学
癌症研究
生物
分子生物学
癌症
氨基酸
遗传学
催化作用
作者
Marc Hennequart,Steven E. Pilley,Christiaan F. Labuschagne,Jack Coomes,Loïc Mervant,Paul C. Driscoll,Nathalie Legrave,Younghwan Lee,Peter Kreuzaler,Benedict Macintyre,Yulia Panina,Julianna Blagih,David Stevenson,Douglas Strathdee,Deborah Schneider-Luftman,Eva Grönroos,Eric C. Cheung,Mariia Yuneva,Charles Swanton,Karen H. Vousden
出处
期刊:Cell Reports
[Elsevier]
日期:2023-06-01
卷期号:42 (6): 112562-112562
被引量:2
标识
DOI:10.1016/j.celrep.2023.112562
摘要
Mitochondrial 10-formyltetrahydrofolate (10-formyl-THF) is utilized by three mitochondrial enzymes to produce formate for nucleotide synthesis, NADPH for antioxidant defense, and formyl-methionine (fMet) to initiate mitochondrial mRNA translation. One of these enzymes—aldehyde dehydrogenase 1 family member 2 (ALDH1L2)—produces NADPH by catabolizing 10-formyl-THF into CO2 and THF. Using breast cancer cell lines, we show that reduction of ALDH1L2 expression increases ROS levels and the production of both formate and fMet. Both depletion of ALDH1L2 and direct exposure to formate result in enhanced cancer cell migration that is dependent on the expression of the formyl-peptide receptor (FPR). In various tumor models, increased ALDH1L2 expression lowers formate and fMet accumulation and limits metastatic capacity, while human breast cancer samples show a consistent reduction of ALDH1L2 expression in metastases. Together, our data suggest that loss of ALDH1L2 can support metastatic progression by promoting formate and fMet production, resulting in enhanced FPR-dependent signaling.
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