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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.

Original publication

DOI

10.1038/s41467-018-03777-w

Type

Journal article

Journal

Nat Commun

Publication Date

10/04/2018

Volume

9

Keywords

Adenoma, Animals, Antimetabolites, Antineoplastic, Cell Line, Tumor, Female, Formates, Gene Expression Regulation, Neoplastic, Glycine Hydroxymethyltransferase, Intestinal Mucosa, Intestinal Neoplasms, Intestines, Isoenzymes, Male, Mammary Glands, Animal, Mammary Neoplasms, Experimental, Mammary Tumor Virus, Mouse, Methotrexate, Mice, Mice, Inbred C57BL, Mitochondria, Oxidation-Reduction, Serine, Tumor Microenvironment