Purine nucleotide depletion prompts cell migration by stimulating the serine synthesis pathway

Mona Hoseini Soflaee, Rushendhiran Kesavan, Umakant Sahu, Alpaslan Tasdogan, Elodie Villa, Zied Djabari, Feng Cai, Diem H. Tran, Hieu S. Vu, Eunus S. Ali, Halie Rion, Brendan P. O’Hara, Sherwin Kelekar, James Hughes Hallett, Misty Martin, Thomas P. Mathews, Peng Gao, John M. Asara, Brendan D. Manning, Issam Ben-SahraGerta Hoxhaj

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Purine nucleotides are necessary for various biological processes related to cell proliferation. Despite their importance in DNA and RNA synthesis, cellular signaling, and energy-dependent reactions, the impact of changes in cellular purine levels on cell physiology remains poorly understood. Here, we find that purine depletion stimulates cell migration, despite effective reduction in cell proliferation. Blocking purine synthesis triggers a shunt of glycolytic carbon into the serine synthesis pathway, which is required for the induction of cell migration upon purine depletion. The stimulation of cell migration upon a reduction in intracellular purines required one-carbon metabolism downstream of de novo serine synthesis. Decreased purine abundance and the subsequent increase in serine synthesis triggers an epithelial-mesenchymal transition (EMT) and, in cancer models, promotes metastatic colonization. Thus, reducing the available pool of intracellular purines re-routes metabolic flux from glycolysis into de novo serine synthesis, a metabolic change that stimulates a program of cell migration.

Original languageEnglish
Article number2698
JournalNature Communications
Volume13
Issue number1
DOIs
StatePublished - Dec 2022

Bibliographical note

Publisher Copyright:
© 2022, The Author(s).

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

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