Fibroblast Growth Factor Receptor 1 Drives the Metastatic Progression of Prostate Cancer

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Metastatic prostate cancer (PCa) lacks curative therapies.
• Fibroblast growth factor (FGF) axis activation is a key mechanism in PCa progression.

Purpose of the Study:

• To investigate the role of fibroblast growth factor receptor 1 (FGFR1) and its isoforms (α/β) in the development of PCa bone metastases.
• To explore the molecular and clinical implications of FGFR1 in PCa pathogenesis.

Main Methods:

• Utilized in silico, in vitro, and in vivo preclinical models.
• Conducted RNA-sequencing and immunohistochemical (IHC) studies on human PCa samples.
• Assessed bone metastases incidence and survival in mice, and analyzed FGFR1 and LAD1 expression in human tissues.

Main Results:

• FGFR1 isoform expression varied across PCa subtypes.
• FGFR1-expressing PC3 cells increased bone metastases and reduced survival in mice.
• Human castration-resistant PCa (CRPC) bone metastases showed significantly enriched FGFR1 expression compared to primary tumors.
• Anchoring filament protein LAD1 expression was elevated in FGFR1-expressing PC3 cells and CRPC bone metastases.

Conclusions:

• FGFR1 expression experimentally induces bone metastases and is enriched in human CRPC bone metastases, indicating a prometastatic role.
• LAD1 is co-enriched in FGFR1-positive CRPC bone metastases, suggesting its involvement in FGFR1-mediated metastasis.
• These findings support FGFR blockade as a potential therapeutic strategy for advanced PCa.