ArticleNature2009
Down's syndrome suppression of tumour growth and the role of the calcineurin inhibitor DSCR1.
Article in Nature, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 185 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.
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Who cites it
185 citing papers in PubMed, 375 citations in OpenAlex.
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- Single-cell multimodal profiling of pan-cancer cell lines uncovers gene regulatory principles underlying intrinsic cell states and environmental features.bioRxiv : the preprint server for biology · 2026Article
- Lifetime risk of solid tumors and leukemia in Down Syndrome: a population-based Swedish matched cohort study.British journal of cancer · 2026Article
- Pulmonary Pseudosequestration in a Child with Down Syndrome.Children (Basel, Switzerland) · 2025Article
- Inducible chromosomal rearrangement reveals nonlinear polygenic dosage effects in driving aneuploid yeast traits.Nature communications · 2025Article
- Cancer and Post-Therapy Cardiotoxicity Risk in Adolescents, Young Adults, and Adults With Down Syndrome.Comprehensive Physiology · 2025Article
- The Hallmarks of Aneuploidy in Cancer and Congenital Syndromes.Annual review of genomics and human genetics · 2025Review
- RCAN1.4 regulates tumor cell engraftment and invasion in a thyroid cancer to lung metastasis-on-a-chip microphysiological system.Biofabrication · 2024Article
- Identification of RCAN1's role in hepatocellular carcinoma using single-cell analysis.BMC cancer · 2024Article
- Cancer, metastasis, and the epigenome.Molecular cancer · 2024Review
- Insights into the Clinical, Biological and Therapeutic Impact of Copy Number Alteration in Cancer.International journal of molecular sciences · 2024Review
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- Therapeutic approaches to CNS diseases via the meningeal lymphatic and glymphatic system: prospects and challenges.Frontiers in cell and developmental biology · 2024Review
- Germline BRCA2 Pathogenic Variant in Primary Breast Cancer of a Down Syndrome Individual.The American journal of case reports · 2023Article
- Isogenic pairs of induced-pluripotent stem-derived endothelial cells identify DYRK1A/PPARG/EGR1 pathway is responsible for Down syndrome-associated pulmonary hypertension.Human molecular genetics · 2023Article
- Down syndrome and leukemia: from basic mechanisms to clinical advances.Haematologica · 2023Review
- TheThyroid : official journal of the American Thyroid Association · 2023Article
- A cancer cell membrane coated, doxorubicin and microRNA co-encapsulated nanoplatform for colorectal cancer theranostics.Molecular therapy oncolytics · 2023Article
- Involvement of an Aberrant Vascular System in Neurodevelopmental, Neuropsychiatric, and Neuro-Degenerative Diseases.Life (Basel, Switzerland) · 2023Review
125 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 8 institutions in 2 countries.
Funding
Abstract
The incidence of many cancer types is significantly reduced in individuals with Down's syndrome, and it is thought that this broad cancer protection is conferred by the increased expression of one or more of the 231 supernumerary genes on the extra copy of chromosome 21. One such gene is Down's syndrome candidate region-1 (DSCR1, also known as RCAN1), which encodes a protein that suppresses vascular endothelial growth factor (VEGF)-mediated angiogenic signalling by the calcineurin pathway. Here we show that DSCR1 is increased in Down's syndrome tissues and in a mouse model of Down's syndrome. Furthermore, we show that the modest increase in expression afforded by a single extra transgenic copy of Dscr1 is sufficient to confer significant suppression of tumour growth in mice, and that such resistance is a consequence of a deficit in tumour angiogenesis arising from suppression of the calcineurin pathway. We also provide evidence that attenuation of calcineurin activity by DSCR1, together with another chromosome 21 gene Dyrk1a, may be sufficient to markedly diminish angiogenesis. These data provide a mechanism for the reduced cancer incidence in Down's syndrome and identify the calcineurin signalling pathway, and its regulators DSCR1 and DYRK1A, as potential therapeutic targets in cancers arising in all individuals.
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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.