ArticleThe Journal of clinical investigation2010
Epigenetic downregulation of human disabled homolog 2 switches TGF-beta from a tumor suppressor to a tumor promoter.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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
60 citing papers in PubMed, 101 citations in OpenAlex.
- Development of a Clinical Assay to Guide Patient Therapy in HPV-Associated Head and Neck Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Identification of serum peptide biomarkers for cholangiocarcinoma diagnosis and staging via MALDI-TOF MS and LC-MS/MS.British journal of cancer · 2026Article
- Article
- Advances and Challenges in Targeting TGF-β Isoforms for Therapeutic Intervention of Cancer: A Mechanism-Based Perspective.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Disabled-2: a protein up-regulated by high molecular weight hyaluronan has both tumor promoting and tumor suppressor roles in ovarian cancer.Cellular and molecular life sciences : CMLS · 2023Article
- Expression Pattern of DAB Adaptor Protein 2 in Left- and Right-Side Colorectal Carcinoma.Genes · 2023Article
- Methyltransferase Inhibition Enables TgfMolecular and cellular biology · 2023Article
- Disabled-2 (International journal of molecular sciences · 2022Review
- Glycoprotein NMB promotes tumor formation and malignant progression of laryngeal squamous cell carcinoma.Cancer science · 2022Article
- Discovering biomarkers for hormone-dependent tumors: in silico study on signaling pathways implicated in cell cycle and cytoskeleton regulation.Molecular genetics and genomics : MGG · 2022Article
- IGFBP-3 and TGF-β inhibit growth in epithelial cells by stimulating type V TGF-β receptor (TβR-V)-mediated tumor suppressor signaling.FASEB bioAdvances · 2021Article
- Short chain fatty acids delay the development of hepatocellular carcinoma in HBx transgenic mice.Neoplasia (New York, N.Y.) · 2021Article
- Loss of CD73 shifts transforming growth factor-β1 (TGF-β1) from tumor suppressor to promoter in endometrial cancer.Cancer letters · 2021Article
- Review
- Prevalence and architecture of posttranscriptionally impaired synonymous mutations in 8,320 genomes across 22 cancer types.Nucleic acids research · 2020Article
- Overexpression of matrix metalloproteinase-9 in breast cancer cell lines remarkably increases the cell malignancy largely via activation of transforming growth factor beta/SMAD signalling.Cell proliferation · 2019Review
- Loss of Disabled-2 Expression in Pancreatic Cancer Progression.Scientific reports · 2019Article
- The role of TGFβ in hematopoiesis and myeloid disorders.Leukemia · 2019Review
- Rapid Downregulation of DAB2 by Toll-Like Receptor Activation Contributes to a Pro-Inflammatory Switch in Activated Dendritic Cells.Frontiers in immunology · 2019Article
- Transforming growth factor-β signaling in head and neck squamous cell carcinoma: Insights into cellular responses.Oncology letters · 2018Review
Corrections and comments
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Authors and funding
28 authors at 11 institutions in 4 countries.
Funding
Abstract
The cytokine TGF-beta acts as a tumor suppressor in normal epithelial cells and during the early stages of tumorigenesis. During malignant progression, cancer cells can switch their response to TGF-beta and use this cytokine as a potent oncogenic factor; however, the mechanistic basis for this is poorly understood. Here we demonstrate that downregulation of disabled homolog 2 (DAB2) gene expression via promoter methylation frequently occurs in human squamous cell carcinomas (SCCs) and acts as an independent predictor of metastasis and poor prognosis. Retrospective microarray analysis in an independent data set indicated that low levels of DAB2 and high levels of TGFB2 expression correlate with poor prognosis. Immunohistochemistry, reexpression, genetic knockout, and RNAi silencing studies demonstrated that downregulation of DAB2 expression modulated the TGF-beta/Smad pathway. Simultaneously, DAB2 downregulation abrogated TGF-beta tumor suppressor function, while enabling TGF-beta tumor-promoting activities. Downregulation of DAB2 blocked TGF-beta-mediated inhibition of cell proliferation and migration and enabled TGF-beta to promote cell motility, anchorage-independent growth, and tumor growth in vivo. Our data indicate that DAB2 acts as a tumor suppressor by dictating tumor cell TGF-beta responses, identify a biomarker for SCC progression, and suggest a means to stratify patients with advanced SCC who may benefit clinically from anti-TGF-beta therapies.
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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.