Increased formate overflow is a hallmark of oxidative cancer

Formate overflow coupled to mitochondrial oxidative metabolism\ has been observed in cancer cell lines, but whether that takes place in the tumor microenvironment is not known. Here we report the observation of serine catabolism to formate in normal murine tissues, with a relative rate correlating w...

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Veröffentlicht in:	Nature communications Jg. 9; H. 1; S. 1368 - 12
Hauptverfasser:	Meiser, Johannes, Schuster, Anne, Pietzke, Matthias, Vande Voorde, Johan, Athineos, Dimitris, Oizel, Kristell, Burgos-Barragan, Guillermo, Wit, Niek, Dhayade, Sandeep, Morton, Jennifer P., Dornier, Emmanuel, Sumpton, David, Mackay, Gillian M., Blyth, Karen, Patel, Ketan J., Niclou, Simone P., Vazquez, Alexei
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	London Nature Publishing Group UK 10.04.2018 Nature Publishing Group Nature Portfolio
Schlagworte:	631/67/2327 631/80/84/2336 631/92/1643 64/110 Adenoma - genetics Adenoma - metabolism Adenoma - pathology Animal models Animals Antimetabolites, Antineoplastic - pharmacology Breast cancer Cancer Catabolism Cell Line, Tumor Female Formates - metabolism Formates - pharmacology Gene Expression Regulation, Neoplastic Glycine Hydroxymethyltransferase - genetics Glycine Hydroxymethyltransferase - metabolism Humanities and Social Sciences Intestinal Mucosa - metabolism Intestinal Neoplasms - genetics Intestinal Neoplasms - metabolism Intestinal Neoplasms - pathology Intestine Intestines - pathology Isoenzymes - genetics Isoenzymes - metabolism Male Mammary gland Mammary Glands, Animal - metabolism Mammary Glands, Animal - pathology Mammary Glands, Animal - virology Mammary Neoplasms, Experimental - drug therapy Mammary Neoplasms, Experimental - genetics Mammary Neoplasms, Experimental - metabolism Mammary Neoplasms, Experimental - virology Mammary Tumor Virus, Mouse - pathogenicity Metabolism Methotrexate - pharmacology Mice Mice, Inbred C57BL Mitochondria Mitochondria - drug effects Mitochondria - metabolism multidisciplinary Overflow Oxidation-Reduction Oxidative metabolism Phenotypes Science Science (multidisciplinary) Serine Serine - metabolism Tumor cell lines Tumor Microenvironment - drug effects
ISSN:	2041-1723, 2041-1723
Online-Zugang:	Volltext
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Zusammenfassung:	Formate overflow coupled to mitochondrial oxidative metabolism\ has been observed in cancer cell lines, but whether that takes place in the tumor microenvironment is not known. Here we report the observation of serine catabolism to formate in normal murine tissues, with a relative rate correlating with serine levels and the tissue oxidative state. Yet, serine catabolism to formate is increased in the transformed tissue of in vivo models of intestinal adenomas and mammary carcinomas. The increased serine catabolism to formate is associated with increased serum formate levels. Finally, we show that inhibition of formate production by genetic interference reduces cancer cell invasion and this phenotype can be rescued by exogenous formate. We conclude that increased formate overflow is a hallmark of oxidative cancers and that high formate levels promote invasion via a yet unknown mechanism. Serine catabolism to formate supplies one-carbon units for biosynthesis. Here the authors show that formate production in murine cancers with high oxidative metabolism exceeds the biosynthetic demand and that high formate levels promotes invasion of cancer cells.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-018-03777-w