ArticleOncotarget2016
MYCN and HDAC5 transcriptionally repress CD9 to trigger invasion and metastasis in neuroblastoma.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
25 citing papers in PubMed, 36 citations in OpenAlex.
- Spatial multi-omics characterization of neuroblastoma reveals ferroptosis-associated metabolic features in high-risk tumors.Genome medicine · 2026Article
- Review
- M344 Suppresses Histone Deacetylase-Associated Phenotypes and Tumor Growth in Neuroblastoma.International journal of molecular sciences · 2025Article
- Molecular regulation and therapeutic targeting ofFrontiers in cell and developmental biology · 2025Review
- Article
- The dual HDAC and PI3K inhibitor, CUDC‑907, inhibits tumor growth and stem‑like properties by suppressing PTX3 in neuroblastoma.International journal of oncology · 2024Article
- Epigenetic Dysregulation inInternational journal of molecular sciences · 2023Review
- Mitotic Dysregulation at Tumor Initiation Creates a Therapeutic Vulnerability to Combination Anti-Mitotic and Pro-Apoptotic Agents for MYCN-Driven Neuroblastoma.International journal of molecular sciences · 2023Article
- Review
- CHD5 inhibits metastasis of neuroblastoma.Oncogene · 2022Article
- MYCN in Neuroblastoma: "Old Wine into New Wineskins".Diseases (Basel, Switzerland) · 2021Review
- Review
- A Chemo-Genomic Approach Identifies Diverse Epigenetic Therapeutic Vulnerabilities in MYCN-Amplified Neuroblastoma.Frontiers in cell and developmental biology · 2021Article
- Insights Into the Function and Clinical Application of HDAC5 in Cancer Management.Frontiers in oncology · 2021Review
- Article
- TSPAN8 as a Novel Emerging Therapeutic Target in Cancer for Monoclonal Antibody Therapy.Biomolecules · 2020Review
- Histone Deacetylases and Histone Deacetylase Inhibitors in Neuroblastoma.Frontiers in cell and developmental biology · 2020Review
- Histone Deacetylase Inhibitors to Overcome Resistance to Targeted and Immuno Therapy in Metastatic Melanoma.Frontiers in cell and developmental biology · 2020Review
- Unscheduled HDAC4 repressive activity in human fibroblasts triggers TP53-dependent senescence and favors cell transformation.Molecular oncology · 2018Article
- Dual BRD4 and AURKA Inhibition Is Synergistic against MYCN-Amplified and Nonamplified Neuroblastoma.Neoplasia (New York, N.Y.) · 2018Article
Corrections and comments
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Authors and funding
40 authors at 16 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The systemic and resistant nature of metastatic neuroblastoma renders it largely incurable with current multimodal treatment. Clinical progression stems mainly from the increasing burden of metastatic colonization. Therapeutically inhibiting the migration-invasion-metastasis cascade would be of great benefit, but the mechanisms driving this cycle are as yet poorly understood. In-depth transcriptome analyses and ChIP-qPCR identified the cell surface glycoprotein, CD9, as a major downstream player and direct target of the recently described GRHL1 tumor suppressor. CD9 is known to block or facilitate cancer cell motility and metastasis dependent upon entity. High-level CD9 expression in primary neuroblastomas correlated with patient survival and established markers for favorable disease. Low-level CD9 expression was an independent risk factor for adverse outcome. MYCN and HDAC5 colocalized to the CD9 promoter and repressed transcription. CD9 expression diminished with progressive tumor development in the TH-MYCN transgenic mouse model for neuroblastoma, and CD9 expression in neuroblastic tumors was far below that in ganglia from wildtype mice. Primary neuroblastomas lacking MYCN amplifications displayed differential CD9 promoter methylation in methyl-CpG-binding domain sequencing analyses, and high-level methylation was associated with advanced stage disease, supporting epigenetic regulation. Inducing CD9 expression in a SH-EP cell model inhibited migration and invasion in Boyden chamber assays. Enforced CD9 expression in neuroblastoma cells transplanted onto chicken chorioallantoic membranes strongly reduced metastasis to embryonic bone marrow. Combined treatment of neuroblastoma cells with HDAC/DNA methyltransferase inhibitors synergistically induced CD9 expression despite hypoxic, metabolic or cytotoxic stress. Our results show CD9 is a critical and indirectly druggable suppressor of the invasion-metastasis cycle in neuroblastoma.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.