FBPase Cancer Research Results

FBPase, Fructose-1,6-Bisphosphatase: Click to Expand ⟱
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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.
Scientific Papers found: Click to Expand⟱
1593- Citrate,    Citrate Induces Apoptotic Cell Death: A Promising Way to Treat Gastric Carcinoma?
- in-vitro, GC, BGC-823 - in-vitro, GC, SGC-7901
PFK↓, citrate, a strong physiological inhibitor of phosphofructokinase (PFK)
Glycolysis↓, citrate is a strong inhibitor of glycolysis
tumCV↓, 10 mM citrate led to a nearly complete disappearance of cancer cells, and after 72 h, no cells remained viable whatever the concentration used
cl‑Casp3↑,
cl‑PARP↑,
Apoptosis↑,
ATP↓, depletion of ATP generated by citrate
ChemoSen↑, In the previous study, citrate sensitized the cells to cisplatin, a drug which was poorly efficient by itself on such cells
Mcl-1↓, In the current study, citrate reduced MCL-1 expression in both the gastric cancer lines in a dose-dependent manner, in agreement with previous observations in mesothelioma cells
glucoNG↑, citrate activates neoglucogenesis by enhancing fructose 1,6-bisphosphatase activity
FBPase↑,
OXPHOS↓, When citrate is abundant in cells, this usually means that energy production (ATP) is sufficient, so oxidative phosphorylation (OXPHOS) and the Krebs cycle are slowed down or stopped.
TCA↓, Krebs cycle are slowed down or stopped.
β-oxidation↓, concomitantly inhibits β-oxidation
HK2↓, It may inhibit HK, at least indirectly, by the physiological retroaction of glucose-6-phosphate (G6P) on HK
PDH↓, citrate may inhibit pyruvate dehydrogenase (PDH) (39), the enzyme of the Krebs cycle which links glycolysis and the tricarboxylic cycle
ROS↑, citrate could also promote the formation of reactive oxygen species (ROS) since a sudden elevation of citrate concentration inside the cell might immediately stimulate the Krebs cycle.

1578- Citrate,    Understanding the Central Role of Citrate in the Metabolism of Cancer Cells and Tumors: An Update
- Review, Var, NA
TCA↑,
FASN↑, Cytosolic acetyl-CoA sustains fatty acid (FA) synthesis (FAS)
Glycolysis↓,
glucoNG↑, while it enhances gluconeogenesis by promoting fructose-1,6-biphosphatase (FBPase)
PFK1↓, citrate directly inhibits the main regulators of glycolysis, phosphofructokinase-1 (PFK1) and phosphofructokinase-2 (PFK2)
PFK2↓, well-known inhibitor of PFK
FBPase↑, enhances gluconeogenesis by promoting fructose-1,6-biphosphatase (FBPase)
TumCP↓, inhibits the proliferation of various cancer cells of solid tumors (human mesothelioma, gastric and ovarian cancer cells) at high concentrations (10–20 mM),
eff↑, promoting apoptosis and the sensitization of cells to cisplatin
ACLY↓, higher concentrations (10 mM or more) decreased both acetylation and ACLY expression
Dose↑, In various cell lines, a high concentration of citrate—generally above 10 mM—inhibits the proliferation of cancer cells in a dose dependent manner
Casp3↑,
Casp2↑,
Casp8↑,
Casp9↑,
Bcl-xL↓,
Mcl-1↓,
IGF-1R↓, citrate at high concentration (10 mM) also inhibits the insulin-like growth factor-1 receptor (IGF-1R)
PI3K↓, pathways
Akt↓, activates PTEN, the key phosphatase inhibiting the PI3K/Akt pathway
mTOR↓,
PTEN↑, high dose of citrate activates PTEN
ChemoSen↑, citrate increases the sensibility of cells to chemotherapy (in particular, cisplatin)
Dose?, oral gavage of citrate sodium (4 g/kg twice a day) for several weeks (4 to 7 weeks) significantly regressed tumors

992- PL,    Piperlongumine based nanomedicine impairs glycolytic metabolism in triple negative breast cancer stem cells through modulation of GAPDH & FBP1
- in-vivo, BC, NA
EPR↓,
Glycolysis↓,
GAPDH↓,
GSTP1/GSTπ↝,
FBPase↑, upregulation of fructose-1,6-bisphosphatase 1 (FBP1), a rate-limiting enzyme in gluconeogenesis.


Showing Research Papers: 1 to 3 of 3

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 3

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

GSTP1/GSTπ↝, 1,   OXPHOS↓, 1,   ROS↑, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 1,  

Core Metabolism/Glycolysis ⓘ

ACLY↓, 1,   FASN↑, 1,   FBPase↑, 3,   GAPDH↓, 1,   glucoNG↑, 2,   Glycolysis↓, 3,   HK2↓, 1,   PDH↓, 1,   PFK↓, 1,   PFK1↓, 1,   PFK2↓, 1,   TCA↓, 1,   TCA↑, 1,   β-oxidation↓, 1,  

Cell Death ⓘ

Akt↓, 1,   Apoptosis↑, 1,   Bcl-xL↓, 1,   Casp2↑, 1,   Casp3↑, 1,   cl‑Casp3↑, 1,   Casp8↑, 1,   Casp9↑, 1,   Mcl-1↓, 2,  

Transcription & Epigenetics ⓘ

tumCV↓, 1,  

DNA Damage & Repair ⓘ

cl‑PARP↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

IGF-1R↓, 1,   mTOR↓, 1,   PI3K↓, 1,   PTEN↑, 1,  

Migration ⓘ

TumCP↓, 1,  

Angiogenesis & Vasculature ⓘ

EPR↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 2,   Dose?, 1,   Dose↑, 1,   eff↑, 1,  
Total Targets: 39

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: FBPase, Fructose-1,6-Bisphosphatase
2 Citric Acid
1 Piperlongumine
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:%  Target#:946  State#:%  Dir#:2
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