ArticleThe Journal of clinical investigation2014
Lineage-specific splicing of a brain-enriched alternative exon promotes glioblastoma progression.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
72 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
- Genetic Variants Impacting Angiogenesis Signaling Pathways in Glioblastoma Multiforme: A Systematic Review of Mutations and Polymorphisms.Current molecular medicine · 2024Pooled it
- Circular RNA MCM3 recruits USP49 to stabilize PTBP1 and promote cisplatin resistance in cervical squamous cell carcinoma.Oncogene · 2026Article
- bayesReact: expression-coupled regulatory motif analysis detects microRNA activity across cancers, tissues, and at the single-cell level.Nucleic acids research · 2026Article
- Alternative splicing: from tumorigenesis to neoantigen-mediated cancer immunotherapy.Biomarker research · 2025Review
- Alternative spliceosomal protein Eftud2 mediated Kif3a exon skipping promotes SHH-subgroup medulloblastoma progression.Cell death and differentiation · 2025Article
- The emerging roles of aberrant alternative splicing in glioma.Cell death discovery · 2025Review
- Long Non-coding RNAs as Key Modulators in Hypoxic-Ischemic Brain Injury: Implications for Neuroprotection.Current pharmaceutical design · 2025Review
- Old players and new insights: unraveling the role of RNA-binding proteins in brain tumors.Theranostics · 2025Review
- PTBP1-mediated repression of neuron-specific CDC42 splicing constitutes a genomic alteration-independent, developmentally conserved vulnerability in IDH-wildtype glioblastoma.Functional & integrative genomics · 2024Article
- Tumour microenvironment programming by an RNA-RNA-binding protein complex creates a druggable vulnerability in IDH-wild-type glioblastoma.Nature cell biology · 2024Article
- The role of annexins in central nervous system development and disease.Journal of molecular medicine (Berlin, Germany) · 2024Review
- MAPP unravels frequent co-regulation of splicing and polyadenylation by RNA-binding proteins and their dysregulation in cancer.Nature communications · 2024Article
- Alternative splicing and related RNA binding proteins in human health and disease.Signal transduction and targeted therapy · 2024Review
- Polypyrimidine Tract Binding Protein: A Universal Player in Cancer Development.Current molecular medicine · 2024Review
- Review
- Review
- Small ankyrin 1 (sANK1) promotes docetaxel resistance in castration-resistant prostate cancer cells by enhancing oxidative phosphorylation.FEBS open bio · 2023Article
- NCell death and differentiation · 2023Article
- Non-coding RNAs and glioma: Focus on cancer stem cells.Molecular therapy oncolytics · 2022Review
- An update on the molecular biology of glioblastoma, with clinical implications and progress in its treatment.Cancer communications (London, England) · 2022Review
12 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
31 authors at 9 institutions in 4 countries.
Funding
Abstract
Tissue-specific alternative splicing is critical for the emergence of tissue identity during development, yet the role of this process in malignant transformation is undefined. Tissue-specific splicing involves evolutionarily conserved, alternative exons that represent only a minority of the total alternative exons identified. Many of these conserved exons have functional features that influence signaling pathways to profound biological effect. Here, we determined that lineage-specific splicing of a brain-enriched cassette exon in the membrane-binding tumor suppressor annexin A7 (ANXA7) diminishes endosomal targeting of the EGFR oncoprotein, consequently enhancing EGFR signaling during brain tumor progression. ANXA7 exon splicing was mediated by the ribonucleoprotein PTBP1, which is normally repressed during neuronal development. PTBP1 was highly expressed in glioblastomas due to loss of a brain-enriched microRNA (miR-124) and to PTBP1 amplification. The alternative ANXA7 splicing trait was present in precursor cells, suggesting that glioblastoma cells inherit the trait from a potential tumor-initiating ancestor and that these cells exploit this trait through accumulation of mutations that enhance EGFR signaling. Our data illustrate that lineage-specific splicing of a tissue-regulated alternative exon in a constituent of an oncogenic pathway eliminates tumor suppressor functions and promotes glioblastoma progression. This paradigm may offer a general model as to how tissue-specific regulatory mechanisms can reprogram normal developmental processes into oncogenic ones.
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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.