Evidence map›Paper›PMID 41630015›Full record

ArticleNeuro-oncology2026

Super-enhancer-driven TCF4 orchestrates neuroblastoma metastasis by sphingolipid-dependent membrane remodeling and ITGB1-FAK activation.

Enzhe Lou, Liling Jiang, Yueyuan Zheng, Ran Zhuo, Huan Zhou, Shiwen Hu, Chunxia Shi, Haichuan Zhang, Xinyue Li, Lizhen Jiang and 6 more

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Article in Neuro-oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

16 authors.

Enzhe LouThe Affiliated Traditional Chinese Medicine Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
Liling JiangGuangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, Sino-French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China.
Yueyuan ZhengThe Affiliated Traditional Chinese Medicine Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.ORCID 0000-0002-5692-8903
Ran ZhuoInstitute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, China.
Huan ZhouGuangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, Sino-French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China.
Shiwen HuGuangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, Sino-French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China.
Chunxia ShiInstitute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, China.
Haichuan ZhangGuangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, Sino-French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China.
Xinyue LiGuangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, Sino-French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China.
Lizhen JiangGuangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, Sino-French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China.
Qiong MaoGuangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, Sino-French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China.
Aochu LiuGuangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, Sino-French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China.
Bingyuan LiuGuangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, Sino-French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China.
Jinxin FangGuangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, Sino-French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China.
Jian PanInstitute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, China.ORCID 0000-0002-0292-5141
Xianping ShiThe Affiliated Traditional Chinese Medicine Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.ORCID 0000-0002-5774-8568

Funding

Guangdong Basic and Applied Basic Research Foundation 2024A1515010703L.L.J. Shenzhen Medical Research Fund B2402019National Natural Science Foundation of China 32200538National Natural Science Foundation of China 82170177/H0809National Natural Science Foundation of China 82303536Natural Science Foundation of Guangdong Province 2023A1515011976Natural Science Foundation of Guangdong Province 2025A1515010451
6 · The paper itself

Abstract

backgroundMetastasis remains a critical determinant of survival in neuroblastoma (NB), yet the role of transcriptional dysregulation, particularly super-enhancer (SE)-mediated transcriptional control in this process has not been elucidated. The aim of this study is to identify the SE-driven transcription factors involved in the metastasis of NB and potential targeted drugs.

methodsThe metastatic SE-driven Transcription Factor 4 (TCF4) was screened and identified by integrating bioinformatic analyses of H3K27ac ChIP-seq and scRNA-seq. The effect of TCF4 on NB cell metastasis was evaluated through in vivo and in vitro functional experiments. The molecular mechanism of TCF4 was investigated by the study of targeted CUT&Tag and transcriptome sequencing.

resultsTCF4 is associated with poor prognosis in patients and significantly promotes the metastasis ability of NB cells both in vivo and in vitro. Mechanistically, TCF4 transcriptionally activates SPTLC1, a pivotal enzyme in sphingolipid biosynthesis, to promote ganglioside GM3 synthesis. GM3 orchestrates membrane architecture remodeling, thereby modulating ITGB1 membrane localization and activation, which subsequently potentiates FAK signaling. Notably, we demonstrate that the HDAC6 inhibitor ACY-1215 suppressed NB malignancy by destabilizing TCF4 protein.

conclusionsOur findings indicate that SE-driven TCF4 can orchestrate metastatic transcriptional networks to maintain NB malignancy and propose ACY-1215 as a translational therapeutic candidate for clinical intervention.

Indexed as

Cell MembraneFocal Adhesion Kinase 1Integrin beta1NeuroblastomaSphingolipidsSuper EnhancersTranscription Factor 4AnimalsCell Line, TumorGene Expression Regulation, NeoplasticHumansMiceTumor Cells, CulturedFocal Adhesion Kinase 1Integrin beta1PTK2 protein, humanSphingolipidsTCF4 protein, humanTranscription Factor 4neuroblastomasuper-enhancertargeted therapiesTCF4transcription factor

Identifiers

PMID41630015
PMCPMC13186455

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