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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Abstract
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 |
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| 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). |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Blyth, Professor Karen and Vazquez, Alexei and Sumpton, Mr David and Mackay, Dr Gillian and Athineos, Mr Dimitris and Dornier, Mr Emmanuel Greg 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 Research |
| ISSN: | 2041-1723 |
| 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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