Fibroblast growth factor pathway promotes glycolysis by activating LDHA and suppressing LDHB in a STAT1-dependent manner in prostate cancer
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View abstract on PubMed
Summary
This summary is machine-generated.Fibroblast growth factor (FGF) signaling promotes prostate cancer (PCa) glycolysis by upregulating lactate dehydrogenase A (LDHA) and downregulating LDHB via STAT1. Inhibiting the FGF pathway suppressed PCa tumor growth.
Area Of Science
- Oncology
- Molecular Biology
- Cancer Metabolism
Background
- Fibroblast growth factor 1 (FGF1) and FGF2 expression dynamics are linked to prostate cancer (PCa) progression.
- Lactate dehydrogenase A (LDHA) and LDHB are key metabolic enzymes influencing tumor growth.
- The interplay between FGF signaling and LDHA/LDHB in PCa-driven glycolysis remains uncharacterized.
Purpose Of The Study
- To investigate if FGF1/FGF2 regulate LDHA and LDHB to promote glycolysis in PCa.
- To elucidate the signaling pathway involved in FGF-mediated glycolysis in PCa progression.
Main Methods
- Utilized in vitro techniques including RT-qPCR, Western blot, CCK-8 assays, and flow cytometry to analyze gene/protein expression, cell viability, apoptosis, and cell cycle in PCa cell lines.
- Assessed glycolysis by measuring glucose consumption, lactate production, and extracellular acidification rate (ECAR).
- Established a PCa xenograft mouse model for in vivo studies, including treatment with an FGF pathway inhibitor and tumor growth monitoring.
Main Results
- FGF1, FGF2, and LDHA were highly expressed in PCa cells, whereas LDHB was lowly expressed.
- FGF1/2 positively modulated LDHA and negatively modulated LDHB, with depletion of FGF1, FGF2, or LDHA inhibiting proliferation and glycolysis.
- FGF1/2 positively regulated STAT1, which transcriptionally activated LDHA and suppressed LDHB; FGF pathway inhibition reduced tumor growth in mice.
Conclusions
- The FGF pathway promotes PCa glycolysis through STAT1-dependent activation of LDHA and suppression of LDHB.
- Targeting the FGF pathway represents a potential therapeutic strategy for inhibiting PCa progression.
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