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Super-enhancer-driven TCF4 promotes neuroblastoma metastasis by mediating GM3 synthesis [CUT&Tag]

GSE303304 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing 3 samples Submitted 2026/05/27 Platform GPL34284
Summary
Metastasis remains a critical factor for survival in neuroblastoma (NB). Although NB metastasis involves multifaceted regulatory mechanisms, the role of epitranscriptomic regulation in this process has not been elucidated. Here, we identify super-enhancer-driven transcription factor TCF4 as a central orchestrator of metastatic networks in NB, promoting both in vitro and in vivo dissemination. Mechanistically, TCF4 transcriptionally activates SPTLC1, a pivotal enzyme in sphingolipid biosynthesis, to promote ganglioside GM3 synthesis. GM3 orchestrates membrane architecture remodeling, thereby modulating ITGB1 membrame localization and activation, which subsequently potentiates metastasis-associated FAK signaling. Notably, we demonstrate that the HDAC6 inhibitor ACY-1215 suppresses NB malignancy by destabilizing TCF4 protein. These findings reveal an epitranscriptomic-metabolic axis governing NB metastasis and propose ACY-1215 as a translational therapeutic candidate for clinical intervention.
Published in
Super-enhancer-driven TCF4 orchestrates neuroblastoma metastasis by sphingolipid-dependent membrane remodeling and ITGB1-FAK activation
Lou E, Jiang L, Zheng Y et al. · Neuro-oncology 2026 · PMID 41630015 · doi:10.1093/neuonc/noag021
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Also filed as BioProject PRJNA1294806 and SRA study SRP602812. Searching any of these in the dataset finder brings you back here.

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