Serine racemase enhances growth of colorectal cancer by producing pyruvate from serine.

Nature Metabolism
Kenji OhshimaEiichi Morii

Abstract

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.

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Citations

May 29, 2021·Scientific Reports·Kento KuritaTakayoshi Suganami

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Datasets Mentioned

BETA
GSE128804

Methods Mentioned

BETA
xenograft
xenografts
PCR
histone acetylation
acetylation
confocal
flow cytometry
transmission electron microscopy
RNA-seq
Assay

Software Mentioned

FlowJo
Cuffnorm
Excel
TopHat
Ingenuity Pathway Analysis ( IPA
JMP Pro
ImageJ

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