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

Szczegóły
Abstrakt

Tytuł:: Serine racemase enhances growth of colorectal cancer by producing pyruvate from serine.
Autorzy:: Ohshima K; Department of Pathology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Nojima S; Department of Pathology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Tahara S; Department of Pathology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Kurashige M; Department of Pathology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Kawasaki K; Department of Pathology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Hori Y; Department of Pathology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Taniguchi M; Department of Biotechnology, Osaka University Graduate School of Engineering, Suita, Osaka, Japan.
Umakoshi Y; Department of Biotechnology, Osaka University Graduate School of Engineering, Suita, Osaka, Japan.
Okuzaki D; Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.; Single Cell Genomics, Human Immunology, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.; Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Osaka, Japan.
Wada N; Department of Pathology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.; Department of Diagnostic Pathology, Osaka City University, Osaka, Osaka, Japan.
Ikeda JI; Department of Diagnostic Pathology, Chiba University Graduate School of Medicine, Chiba, Chiba, Japan.
Fukusaki E; Department of Biotechnology, Osaka University Graduate School of Engineering, Suita, Osaka, Japan.
Morii E; Department of Pathology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. .
Źródło:: Nature metabolism [Nat Metab] 2020 Jan; Vol. 2 (1), pp. 81-96. Date of Electronic Publication: 2020 Jan 13.
Typ publikacji:: Journal Article; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Original Publication: Berlin : Springer Nature, [2019]-
MeSH Terms:: Cell Proliferation*
Colorectal Neoplasms/*pathology
Pyruvic Acid/*metabolism
Racemases and Epimerases/*metabolism
Serine/*metabolism
Animals ; Cell Line, Tumor ; Colorectal Neoplasms/metabolism ; Heterografts ; Humans ; Mice ; Mice, Nude ; RNA, Messenger/genetics ; Racemases and Epimerases/genetics ; Up-Regulation
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Substance Nomenclature:: 0 (RNA, Messenger)
452VLY9402 (Serine)
8558G7RUTR (Pyruvic Acid)
EC 5.1.- (Racemases and Epimerases)
EC 5.1.1.16 (serine racemase)
Entry Date(s):: Date Created: 20200723 Date Completed: 20210119 Latest Revision: 20210119
Update Code:: 20240104
DOI:: 10.1038/s42255-019-0156-2
PMID:: 32694681
: Czasopismo naukowe

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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