Increased formate overflow is a hallmark of oxidative cancer. Academic Article uri icon

Overview

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.

publication date

  • April 10, 2018

Research

keywords

  • Adenoma
  • Formates
  • Gene Expression Regulation, Neoplastic
  • Intestinal Neoplasms
  • Mammary Neoplasms, Experimental
  • Serine

Identity

PubMed Central ID

  • PMC5893600

Scopus Document Identifier

  • 85045238581

Digital Object Identifier (DOI)

  • 10.1038/s41467-018-03777-w

PubMed ID

  • 29636461

Additional Document Info

volume

  • 9

issue

  • 1