ArticleCancer immunology research2013
Novel mechanism of tumor suppression by polarity gene discs large 1 (DLG1) revealed in a murine model of pediatric B-ALL.
Article in Cancer immunology research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 24 citations in OpenAlex.
- KDM5B promotes SMAD4 loss-driven drug resistance through activating DLG1/YAP to induce lipid accumulation in pancreatic ductal adenocarcinoma.Cell death discovery · 2024Article
- LINC01315 Impairs microRNA-211-Dependent DLG3 Downregulation to Inhibit the Development of Oral Squamous Cell Carcinoma.Frontiers in oncology · 2020Article
- High expression of DLG3 is associated with decreased survival from breast cancer.Clinical and experimental pharmacology & physiology · 2019Article
- Dlg1 Maintains Dendritic Cell Function by Securing Voltage-Gated KJournal of immunology (Baltimore, Md. : 1950) · 2019Article
- Acidification of Tumor at Stromal Boundaries Drives Transcriptome Alterations Associated with Aggressive Phenotypes.Cancer research · 2019Article
- Influence of Scribble polarity complex on hematopoiesis and leukemia - a matter of where, when and how.Oncotarget · 2018Article
- The functions and regulation of the PTEN tumour suppressor: new modes and prospects.Nature reviews. Molecular cell biology · 2018Review
- Long Non Coding RNA Expression Intersecting Cancer and Spermatogenesis: A Systematic ReviewAsian Pacific journal of cancer prevention : APJCP · 2017Article
- Scribble acts as an oncogene in Eμ-myc-driven lymphoma.Oncogene · 2016Article
- Adenovirus E4-ORF1 Dysregulates Epidermal Growth Factor and Insulin/Insulin-Like Growth Factor Receptors To Mediate Constitutive Myc Expression.Journal of virology · 2015Article
- Functionally distinct PI 3-kinase pathways regulate myelination in the peripheral nervous system.The Journal of cell biology · 2014Article
- Polarized cells, polarized views: asymmetric cell division in hematopoietic cells.Frontiers in immunology · 2014Review
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Drosophila melanogaster discs large (dlg) is an essential tumor suppressor gene (TSG) controlling epithelial cell growth and polarity of the fly imaginal discs in pupal development. A mammalian ortholog, Dlg1, is involved in embryonic urogenital morphogenesis, postsynaptic densities in neurons, and immune synapses in lymphocytes. However, a potential role for Dlg1 as a mammalian TSG is unknown. Here, we present evidence that loss of Dlg1 confers strong predisposition to the development of malignancies in a murine model of pediatric B-cell acute lymphoblastic leukemia (B-ALL). Using mice with conditionally deleted Dlg1 alleles, we identify a novel "pre-leukemic" stage of developmentally arrested early B-lineage cells marked by preeminent c-Myc expression. Mechanistically, we show that in B-lineage progenitors Dlg1 interacts with and stabilizes the PTEN protein, regulating its half-life and steady-state abundance. The loss of Dlg1 does not affect the level of PTEN mRNAs but results in a dramatic decrease in PTEN protein, leading to excessive phosphoinositide 3-kinase signaling and proliferation. Our data suggest a novel model of tumor suppression by a PDZ domain-containing polarity gene in hematopoietic cancers.
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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.