Increased formate overflow is a hallmark of oxidative cancer

Meiser, J. et al. (2018) Increased formate overflow is a hallmark of oxidative cancer. Nature Communications, 9, 1368. (doi: 10.1038/s41467-018-03777-w) (PMID:29636461) (PMCID:PMC5893600)

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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.

Item Type:Articles
Additional Information:This work was supported by Cancer Research UK C596/A21140. J.M. was supported by a DFG Fellowship Grant Number: ME 4636/2-1. We acknowledge the Cancer Research UK Glasgow Center (C596/A18076) and the BSU facilities at the Cancer Research UK Beatson Institute (C596/A17196). A.S. was supported by Fondation Cancer Luxembourg (INVGBM project).
Glasgow Author(s) Enlighten ID:Blyth, Professor Karen and Sumpton, Mr David and Dornier, Mr Emmanuel Greg and Vazquez, Alexei and Mackay, Dr Gillian and Athineos, Mr Dimitris and Morton, Professor Jen
Authors: Meiser, J., Schuster, A., Pietzke, M., Voore, J. V., Athineos, D., Oizel, K., Burgos-Barragan, G., Wit, N., Dhayade, S., Morton, J. P., Dornier, E., Sumpton, D., Mackay, G. M., Blyth, K., Patel, K. J., Niclou, S. P., and Vazquez, A.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
Journal Name:Nature Communications
Publisher:Nature Publishing Group
ISSN (Online):2041-1723
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Nature Communications 9: 1368
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
647981CR-UK Centre renewalKaren VousdenCancer Research UK (CRUK)18076RI CANCER SCIENCES