FUT8 Is a Critical Driver of Prostate Tumour Growth and Can Be Targeted Using Fucosylation Inhibitors

Area of Science:

• Oncology
• Glycobiology
• Cancer Therapeutics

Background:

• Aberrant glycosylation is a hallmark of cancer, influencing tumor progression, immune evasion, and metastasis.
• Prostate cancer progression is linked to altered tumor glycosylation, highlighting glycans as potential therapeutic targets.
• Fucosyltransferase 8 (FUT8) mediates core fucosylation, a process implicated in cancer, but its specific role in prostate cancer is unclear.

Purpose of the Study:

• To investigate the role of FUT8 in prostate cancer progression.
• To determine if FUT8 activity correlates with disease aggressiveness.
• To explore the therapeutic potential of targeting FUT8 in prostate cancer.

Main Methods:

• Analysis of FUT8 expression in clinical prostate cancer cohorts.
• Utilized PhosL lectin immunofluorescence and N-glycan MALDI mass spectrometry imaging (MALDI-MSI).
• Employed in vitro and in vivo models to assess FUT8 function and the efficacy of fucosylation inhibitors.

Main Results:

• FUT8 is upregulated in high-grade and metastatic prostate tumors and in patients with aggressive disease.
• FUT8 drives the biosynthesis of malignant core fucosylated N-glycans in prostate cancer cells.
• FUT8 promotes prostate tumor growth, cell motility, and invasion by regulating key signaling pathways.
• Fucosylation inhibitors effectively suppressed FUT8 activity and prostate tumor growth in preclinical models.

Conclusions:

• FUT8-mediated core fucosylation is a significant driver of prostate cancer progression.
• Targeting FUT8 represents a promising therapeutic strategy for advanced prostate cancer.