2. Academic Validation
  3. Purine nucleotide depletion prompts cell migration by stimulating the serine synthesis pathway

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

  • Nat Commun. 2022 May 16;13(1):2698. doi: 10.1038/s41467-022-30362-z.
Mona Hoseini Soflaee  # 1,  Rushendhiran Kesavan  # 1,  Umakant Sahu  # 2 3,  Alpaslan Tasdogan 4,  Elodie Villa 2 3,  Zied Djabari 2 3,  Feng Cai 1,  Diem H Tran 1,  Hieu S Vu 1,  Eunus S Ali 2 3,  Halie Rion 1,  Brendan P O'Hara 2 3,  Sherwin Kelekar 1,  James Hughes Hallett 5,  Misty Martin 1,  Thomas P Mathews 1,  Peng Gao 6,  John M Asara 7,  Brendan D Manning 8,  Issam Ben-Sahra 9 10,  Gerta Hoxhaj 11
Affiliations

Affiliations

  • 1 Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, 75390, USA.
  • 2 Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
  • 3 Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, 60611, USA.
  • 4 Department of Dermatology, University Hospital Essen & German Cancer Consortium, Partner Site, Essen, Germany.
  • 5 Department of Molecular Metabolism, Harvard T. H. Chan School of Public Health, Boston, MA, 02115, USA.
  • 6 Metabolomics Core Facility, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, 60611, USA.
  • 7 Mass Spectrometry Core, Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA.
  • 8 Department of Molecular Metabolism, Harvard T. H. Chan School of Public Health, Boston, MA, 02115, USA. bmanning@hsph.harvard.edu.
  • 9 Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA. issam.ben-sahra@northwestern.edu.
  • 10 Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, 60611, USA. issam.ben-sahra@northwestern.edu.
  • 11 Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, 75390, USA. gerta.hoxhaj@utsouthwestern.edu.
  • # Contributed equally.
PMID: 35577785 DOI: 10.1038/s41467-022-30362-z
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.

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