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

• DOI: 10.1038/s41467-022-30362-z
• Publication Date: 2022-05-16T10:03:26Z
• Authors: 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-Sahra; Gerta Hoxhaj
• Keywords: Purine metabolism; De novo synthesis; Metabolic pathway

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