Abstract
We propose that fructose-1,6-bisphosphate (F-1,6-BP) promotes a feedback loop between phosphofructokinase-1 (PFK1), phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt), and PFK2/PFKFB3, which enhances aerobic glycolysis and sustains effector T (Teff) cell activation, while oxidative metabolism is concomitantly downregulated. This regulation, promoted by low citrate and mitochondrial ATP synthesis, also sustains the Warburg effect in cancer cells.
Keywords:
T cell; Warburg effect; cancer cell; citrate; fructose-1,6-bisphosphate; metabolism.
Copyright © 2021 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphate / biosynthesis
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Citric Acid
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Fructosediphosphates / metabolism*
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Glycolysis*
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Lymphocyte Activation
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Mitochondria
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Neoplasms
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Phosphatidylinositol 3-Kinases / genetics
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphofructokinase-1* / genetics
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Phosphofructokinase-1* / metabolism
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Proto-Oncogene Proteins c-akt / genetics
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Proto-Oncogene Proteins c-akt / metabolism
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T-Lymphocytes* / metabolism
Substances
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Fructosediphosphates
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Citric Acid
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Adenosine Triphosphate
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Phosphofructokinase-1
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Proto-Oncogene Proteins c-akt
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fructose-1,6-diphosphate