ArticleMolecular cancer2015
Oncogenic KRAS promotes malignant brain tumors in zebrafish.
Article in Molecular cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 67 citations in OpenAlex.
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- From benign neurofibromas to malignant peripheral nerve sheath tumors (MPNST): a gaming among multiple factors.Cellular oncology (Dordrecht, Netherlands) · 2025Review
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- Small Fish, Big Answers: Zebrafish and the Molecular Drivers of Metastasis.International journal of molecular sciences · 2025Review
- Zebrafish models in glioma research: advances in methodologies, mechanistic insights, and therapeutic frontiers.Frontiers in immunology · 2025Review
- A syngeneic spontaneous zebrafish model ofeLife · 2024Article
- Modeling of brain tumors usingHeliyon · 2024Review
- IL-1β disrupts the initiation of blood-brain barrier development by inhibiting endothelial Wnt/β-catenin signaling.iScience · 2024Article
- Zebrafish-based platform for emerging bio-contaminants and virus inactivation research.The Science of the total environment · 2023Review
- Combined Inhibition of Hedgehog and HDAC6: In Vitro and In Vivo Studies Reveal a New Role for Lysosomal Stress in Reducing Glioblastoma Cell Viability.International journal of molecular sciences · 2023Article
- Zebrafish Models of Paediatric Brain Tumours.International journal of molecular sciences · 2022Review
- Emerging Roles of RNA-Binding Proteins in Neurodevelopment.Journal of developmental biology · 2022Review
- Real-time evaluation of glioblastoma growth in patient-specific zebrafish xenografts.Neuro-oncology · 2022Article
- What Zebrafish and Nanotechnology Can Offer for Cancer Treatments in the Age of Personalized Medicine.Cancers · 2022Review
- Exposure to trace levels of metals and fluoroquinolones increases inflammation and tumorigenesis risk of zebrafish embryos.Environmental science and ecotechnology · 2022Article
- Article
- Modeling Brain Tumors: A Perspective Overview ofFrontiers in molecular neuroscience · 2022Review
- Modeling human brain tumors in flies, worms, and zebrafish: From proof of principle to novel therapeutic targets.Neuro-oncology · 2021Review
- Cellular and Molecular Mechanisms Underlying Glioblastoma and Zebrafish Models for the Discovery of New Treatments.Cancers · 2021Review
- Tipping the Scales With Zebrafish to Understand Adaptive Tumor Immunity.Frontiers in cell and developmental biology · 2021Review
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundZebrafish have been used as a vertebrate model to study human cancers such as melanoma, rhabdomyosarcoma, liver cancer, and leukemia as well as for high-throughput screening of small molecules of therapeutic value. However, they are just emerging as a model for human brain tumors, which are among the most devastating and difficult to treat. In this study, we evaluated zebrafish as a brain tumor model by overexpressing a human version of oncogenic KRAS (KRAS(G12V)).
methodsUsing zebrafish cytokeratin 5 (krt5) and glial fibrillary acidic protein (gfap) gene promoters, we activated Ras signaling in the zebrafish central nervous system (CNS) through transient and stable transgenic overexpression. Immunohistochemical analyses were performed to identify activated pathways in the resulting brain tumors. The effects of the MEK inhibitor U0126 on oncogenic KRAS were evaluated.
resultsWe demonstrated that transient transgenic expression of KRAS(G12V) in putative neural stem and/or progenitor cells induced brain tumorigenesis. When expressed under the control of the krt5 gene promoter, KRAS(G12V) induced brain tumors in ventricular zones (VZ) at low frequency. The majority of other tumors were composed mostly of spindle and epithelioid cells, reminiscent of malignant peripheral nerve sheath tumors (MPNSTs). In contrast, when expressed under the control of the gfap gene promoter, KRAS(G12V) induced brain tumors in both VZs and brain parenchyma at higher frequency. Immunohistochemical analyses indicated prominent activation of the canonical RAS-RAF-ERK pathway, variable activation of the mTOR pathway, but no activation of the PI3K-AKT pathway. In a krt5-derived stable and inducible transgenic line, expression of oncogenic KRAS resulted in skin hyperplasia, and the MEK inhibitor U0126 effectively suppressed this pro-proliferative effects. In a gfap-derived stable and inducible line, expression of oncogenic KRAS led to significantly increased mitotic index in the spinal cord.
conclusionsOur studies demonstrate that zebrafish could be explored to study cellular origins and molecular mechanisms of brain tumorigenesis and could also be used as a platform for studying human oncogene function and for discovering oncogenic RAS inhibitors.
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