Fibroblast growth factor pathway promotes glycolysis by activating LDHA and suppressing LDHB in a STAT1-dependent...

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.