ArticleCancer research2016
Drosophila Brat and Human Ortholog TRIM3 Maintain Stem Cell Equilibrium and Suppress Brain Tumorigenesis by Attenuating Notch Nuclear Transport.
Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35 citing papers in PubMed, 52 citations in OpenAlex.
- Review
- Tumor-suppressive activities of SA1/STAG2 and effects of PARP impairment during brain development.Disease models & mechanisms · 2026Article
- Article
- Laboratory and physiological aspects of substitute metazoan models for in vivo pharmacotoxicological analysis.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Unveiling the Tumor Suppressors: Insights from Drosophila.Advances in experimental medicine and biology · 2025Review
- Tripartite-motif 3 represses ovarian cancer progression by downregulating lactate dehydrogenase A and inhibiting AKT signaling.Molecular and cellular biochemistry · 2024Article
- Advances in the antitumor mechanisms of tripartite motif-containing protein 3.Journal of cancer research and clinical oncology · 2024Review
- Ribogenesis boosts controlled by HEATR1-MYC interplay promote transition into brain tumour growth.EMBO reports · 2024Article
- Regenerative growth is constrained by brain tumor to ensure proper patterning in Drosophila.PLoS genetics · 2023Article
- LST-1 is a bifunctional regulator that feeds back on Notch-dependent transcription to regulateProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Growth deregulation and interaction with host hemocytes contribute to tumor progression in a Drosophila brain tumor model.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Dual roles of TRIM3 in colorectal cancer by retaining p53 in the cytoplasm to decrease its nuclear expression.Cell death discovery · 2023Article
- Modelling Cancer Metastasis inCells · 2023Review
- TRIM56 promotes malignant progression of glioblastoma by stabilizing cIAP1 protein.Journal of experimental & clinical cancer research : CR · 2022Article
- Review
- Tripartite Motif Containing 3 inhibits the aggressive behaviors of papillary thyroid carcinoma and indicates lower recurrence risk.Genes & genomics · 2022Article
- Pre-clinical models for evaluating glioma targeted immunotherapies.Frontiers in immunology · 2022Review
- Review
- Tripartite motif-containing 3 (TRIM3) enhances ER signaling and confers tamoxifen resistance in breast cancer.Oncogenesis · 2021Article
- Molecular and biological functions of TRIM-NHL RNA-binding proteins.Wiley interdisciplinary reviews. RNA · 2021Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Cancer stem cells exert enormous influence on neoplastic behavior, in part by governing asymmetric cell division and the balance between self-renewal and multipotent differentiation. Growth is favored by deregulated stem cell division, which enhances the self-renewing population and diminishes the differentiation program. Mutation of a single gene in Drosophila, Brain Tumor (Brat), leads to disrupted asymmetric cell division resulting in dramatic neoplastic proliferation of neuroblasts and massive larval brain overgrowth. To uncover the mechanisms relevant to deregulated cell division in human glioma stem cells, we first developed a novel adult Drosophila brain tumor model using brat-RNAi driven by the neuroblast-specific promoter inscuteable Suppressing Brat in this population led to the accumulation of actively proliferating neuroblasts and a lethal brain tumor phenotype. brat-RNAi caused upregulation of Notch signaling, a node critical for self-renewal, by increasing protein expression and enhancing nuclear transport of Notch intracellular domain (NICD). In human glioblastoma, we demonstrated that the human ortholog of Drosophila Brat, tripartite motif-containing protein 3 (TRIM3), similarly suppressed NOTCH1 signaling and markedly attenuated the stem cell component. We also found that TRIM3 suppressed nuclear transport of active NOTCH1 (NICD) in glioblastoma and demonstrated that these effects are mediated by direct binding of TRIM3 to the Importin complex. Together, our results support a novel role for Brat/TRIM3 in maintaining stem cell equilibrium and suppressing tumor growth by regulating NICD nuclear transport. Cancer Res; 76(8); 2443-52. ©2016 AACR.
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