TY - JOUR
T1 - Purine nucleotide depletion prompts cell migration by stimulating the serine synthesis pathway
AU - Soflaee, Mona Hoseini
AU - Kesavan, Rushendhiran
AU - Sahu, Umakant
AU - Tasdogan, Alpaslan
AU - Villa, Elodie
AU - Djabari, Zied
AU - Cai, Feng
AU - Tran, Diem H.
AU - Vu, Hieu S.
AU - Ali, Eunus S.
AU - Rion, Halie
AU - O’Hara, Brendan P.
AU - Kelekar, Sherwin
AU - Hallett, James Hughes
AU - Martin, Misty
AU - Mathews, Thomas P.
AU - Gao, Peng
AU - Asara, John M.
AU - Manning, Brendan D.
AU - Ben-Sahra, Issam
AU - Hoxhaj, Gerta
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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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U2 - 10.1038/s41467-022-30362-z
DO - 10.1038/s41467-022-30362-z
M3 - Article
C2 - 35577785
AN - SCOPUS:85130050044
SN - 2041-1723
VL - 13
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 2698
ER -