2020年1月13日
Serine racemase enhances growth of colorectal cancer by producing pyruvate from serine
Nature Metabolism
- 巻
- 2
- 号
- 1
- 開始ページ
- 81
- 終了ページ
- 96
- 記述言語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1038/s42255-019-0156-2
© 2020, The Author(s), under exclusive licence to Springer Nature Limited. Serine racemase (SRR) catalyses not only the racemization but also the dehydration of l-serine and d-serine, resulting in the formation of pyruvate and ammonia. Although SRR activity is important in the central nervous system, SRR has not been linked to cancer metabolism before. Here we show that SRR supports proliferation of colorectal-cancer cells. We find that SRR expression is upregulated in colorectal adenoma and adenocarcinoma lesions compared with non-neoplastic mucosa in human colorectal-cancer specimens. SRR-mediated dehydration of serine contributes to the pyruvate pool in colon-cancer cells, enhances proliferation, maintains mitochondrial mass and increases basal reactive oxygen species production, which has anti-apoptotic effects. Moreover, SRR promotes acetylation of histone H3 by maintaining intracellular acetyl-CoA levels. Inhibition of SRR suppresses growth of colorectal tumours in mice and augments the efficacy of 5-fluorouracil treatment. Our findings highlight a previously unknown mechanism through which a racemase supports cancer-cell growth and suggest that SRR might be a molecular target for colorectal-cancer therapy.
- リンク情報
- ID情報
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- DOI : 10.1038/s42255-019-0156-2
- eISSN : 2522-5812
- SCOPUS ID : 85077860826