Fructose-1,6-bisphosphatase (FBPase) is a key enzyme of gluconeogenesis that has garnered significant attention in cancer research. Altered metabolic pathways are hallmarks of cancer, and many tumors rely on aerobic glycolysis (the Warburg effect) rather than oxidative phosphorylation even in the presence of oxygen. In this context, the expression and activity of FBPase—primarily FBP1 and to some extent FBP2—play important roles in modulating cancer metabolism as well as impacting patient prognosis.
FBP1 (Fructose-1,6-Bisphosphatase 1) is a key enzyme in gluconeogenesis, the process by which cells generate glucose from non-carbohydrate sources. FBP1 is often downregulated in cancer cells, and its low expression is associated with poor prognosis.
FBP1 is a key enzyme in the regulation of the Warburg effect, a metabolic phenomenon in which cancer cells preferentially use glycolysis for energy production, even in the presence of oxygen.
FBP1 activators are being developed as a potential therapeutic strategy for cancer treatment.
Key Role in Gluconeogenesis
-FBPase catalyzes the conversion of fructose-1,6-bisphosphate to fructose-6-phosphate, which is a pivotal step in gluconeogenesis.
-This counteracts glycolysis—a pathway often upregulated in cancer cells to support rapid proliferation and biomass generation.
Altered FBPase Expression in Cancer
-A decrease or loss of FBP1 expression has been observed in several cancer types
FBP1:
-Primarily found in the liver and kidney.
-Plays a central role in gluconeogenesis by catalyzing the conversion of fructose-1,6-bisphosphate to fructose-6-phosphate.
-Its expression is more frequently linked to altered metabolic states in various cancers (e.g., reduced FBP1 is often associated with a glycolytic and more aggressive tumor metabolism).
FBP2:
-Known as the muscle isoform of fructose-1,6-bisphosphatase.
-While it performs a similar catalytic function, its expression profile and regulation differ from FBP1 and it is less commonly associated with the metabolic rewiring observed in many cancers.
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