Formate promotes invasion and metastasis in reliance on lipid metabolism

Catherine Delbrouck, Nicole Kiweler, Oleg Chen, Vitaly I. Pozdeev, Lara Haase, Laura Neises, Anaïs Oudin, Aymeric Fouquier d'Hérouël, Ruolin Shen, Lisa Schlicker, Rashi Halder, Antoine Lesur, Anne Schuster, Nadja I. Lorenz, Christian Jaeger, Maureen Feucherolles, Gilles Frache, Martyna Szpakowska, Andy Chevigne, Michael W. RonellenfitschEtienne Moussay, Marie Piraud, Alexander Skupin, Almut Schulze, Simone P. Niclou, Elisabeth Letellier, Johannes Meiser*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)

Abstract

Metabolic rewiring is essential for cancer onset and progression. We previously showed that one-carbon metabolism-dependent formate production often exceeds the anabolic demand of cancer cells, resulting in formate overflow. Furthermore, we showed that increased extracellular formate concentrations promote the in vitro invasiveness of glioblastoma cells. Here, we substantiate these initial observations with ex vivo and in vivo experiments. We also show that exposure to exogeneous formate can prime cancer cells toward a pro-invasive phenotype leading to increased metastasis formation in vivo. Our results suggest that the increased local formate concentration within the tumor microenvironment can be one factor to promote metastases. Additionally, we describe a mechanistic interplay between formate-dependent increased invasiveness and adaptations of lipid metabolism and matrix metalloproteinase activity. Our findings consolidate the role of formate as pro-invasive metabolite and warrant further research to better understand the interplay between formate and lipid metabolism.

Original languageEnglish
Article number113034
JournalCell Reports
Volume42
Issue number9
Early online date30 Aug 2023
DOIs
Publication statusPublished - 26 Sept 2023

Keywords

  • cancer metastasis
  • CP: Cancer
  • CP: Metabolism
  • formate overflow
  • invasion
  • one-carbon metabolism

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