ArticleEndocrinology2008
Insulin receptor substrate-1 deficiency promotes apoptosis in the putative intestinal crypt stem cell region, limits Apcmin/+ tumors, and regulates Sox9.
Article in Endocrinology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 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.
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Who cites it
31 citing papers in PubMed, 48 citations in OpenAlex.
- Uncovering the function of insulin receptor substrate in termites' immunity through active immunization.Journal of insect science (Online) · 2024Article
- Type 2 inflammation drives an airway basal stem cell program through insulin receptor substrate signaling.The Journal of allergy and clinical immunology · 2023Article
- Prenatal stress induces changes in PAR2- and M3-dependent regulation of colon primitive cells.American journal of physiology. Gastrointestinal and liver physiology · 2022Article
- Insulin receptor substrate 1 may play divergent roles in human colorectal cancer development and progression.World journal of gastroenterology · 2020Article
- Role of anabolic agents in colorectal carcinogenesis: Myths and realities (Review).Oncology reports · 2019Review
- Insulin-like Growth Factor II: An Essential Adult Stem Cell Niche Constituent in Brain and Intestine.Stem cell reports · 2019Article
- Quantitative proteomic profiling of primary cancer-associated fibroblasts in oesophageal adenocarcinoma.British journal of cancer · 2018Article
- Comparative transcriptomic analysis of skeletal muscle tissue during prenatal stages in Tongcheng and Yorkshire pig using RNA-seq.Functional & integrative genomics · 2018Article
- Article
- TGFβ/Smad3 regulates proliferation and apoptosis through IRS-1 inhibition in colon cancer cells.PloS one · 2017Article
- Targeting colorectal cancer via its microenvironment by inhibiting IGF-1 receptor-insulin receptor substrate and STAT3 signaling.Oncogene · 2016Article
- The evolving roles of canonical WNT signaling in stem cells and tumorigenesis: implications in targeted cancer therapies.Laboratory investigation; a journal of technical methods and pathology · 2016Article
- miR-628 Promotes Burn-Induced Skeletal Muscle Atrophy via Targeting IRS1.International journal of biological sciences · 2016Article
- Elp3 drives Wnt-dependent tumor initiation and regeneration in the intestine.The Journal of experimental medicine · 2015Article
- Obesity and intestinal epithelial deletion of the insulin receptor, but not the IGF 1 receptor, affect radiation-induced apoptosis in colon.American journal of physiology. Gastrointestinal and liver physiology · 2015Article
- Islet formation in mice and men: lessons for the generation of functional insulin-producing β-cells from human pluripotent stem cells.Current opinion in genetics & development · 2015Review
- Tumor suppressors miR-143 and miR-145 and predicted target proteins API5, ERK5, K-RAS, and IRS-1 are differentially expressed in proximal and distal colon.American journal of physiology. Gastrointestinal and liver physiology · 2015Article
- The Novel Functions of High-Molecular-Mass Complexes Containing Insulin Receptor Substrates in Mediation and Modulation of Insulin-Like Activities: Emerging Concept of Diverse Functions by IRS-Associated Proteins.Frontiers in endocrinology · 2015Review
- Novel insulin receptor substrate 1 and 2 variants in breast and colorectal cancer.Oncology reports · 2013Article
- SOX9 expression and its methylation status in gastric cancer.Virchows Archiv : an international journal of pathology · 2012Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Reduced apoptosis of crypt stem/progenitor cells and elevated insulin and IGFs are linked to colon cancer risk. Insulin receptor substrate-1 (IRS-1) mediates the actions of insulin, IGF-I, and IGF-II, but the role of endogenous IRS-1 in crypt apoptosis and cancer is undefined. Using IRS-1(-/-), IRS-1(+/-), and IRS-1(+/+) mice, we tested the hypothesis that reduced IRS-1 expression increases apoptosis of intestinal crypt cells and protects against Apc(min/+) (Min)/beta-catenin-driven intestinal tumors. Expression of Sox9, a transcriptional target of Tcf/beta-catenin and putative biomarker of crypt stem cells, was assessed in intestine of different IRS-1 genotypes and cell lines. Irradiation-induced apoptosis was significantly increased in the crypts and crypt stem cell region of IRS-1-deficient mice. Tumor load was significantly reduced by 31.2 +/- 14.6% in IRS-1(+/-)/Min and by 64.1 +/- 7.6% in IRS-1(-/-)/Min mice, with more prominent reductions in tumor number than size. Compared with IRS-1(+/+)/Min, IRS-1(-/-)/Min mice had fewer Sox9-positive cells in intestinal crypts and reduced Sox9 mRNA in intestine. IRS-1 overexpression increased Sox9 expression in an intestinal epithelial cell line. We conclude that even small reductions in endogenous IRS-1 increase apoptosis of crypt stem or progenitor cells, protect against beta-catenin-driven intestinal tumors, and reduce Sox9, a Tcf/beta-catenin target and putative stem/progenitor cell biomarker.
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What OpenQuestion holds
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.