FUCA1-Mediated Metabolic Adaptation Facilitates Lactylation-Induced Vasculogenic Mimicry in Glioblastoma.

FUCA1-mediated glycolysis-linked histone H3K18 lactylation drives vasculogenic mimicry in glioblastoma stem-like cells, with DFH significantly reducing GSC tumorigenicity and VM in vivo.

• Why it matters: VM enables perfusable vascular channels independent of endothelial cells and is linked to resistance against VEGFA-targeted therapy in cancer, including glioblastoma.
• What they did: Using organ-scale vascular imaging, the study found FUCA1 preferentially expressed in CD44-high GSCs; FUCA1 stabilized LDHA, increased glycolytic flux and lactate, and promoted H3K18la to activate SERPINF1 transcription.
• The result: In preclinical models, the FUCA1 inhibitor deoxyfuconojirimycin hydrochloride (DFH) significantly reduced GSC tumorigenicity and VM in vivo and showed robust antitumor activity when combined with anti-VEGFA therapy.

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