Increased formate overflow is a hallmark of oxidative cancer

Johannes Meiser, Anne Schuster, Matthias Pietzke, Johan Vande Voorde, Dimitris Athineos, Kristell Oizel, Guillermo Burgos-Barragan, Niek Wit, Sandeep Dhayade, Jennifer P. Morton, Emmanuel Dornier, David Sumpton, Gillian M. Mackay, Karen Blyth, Ketan J. Patel, Simone P. Niclou, Alexei Vazquez*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

46 Citations (Scopus)

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.

Original languageEnglish
Article number1368
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - 1 Dec 2018

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