ArticlePloS one2013
Effect of IRS4 levels on PI 3-kinase signalling.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Genetic architecture of mammographic density as a risk factor for breast cancer: a systematic review.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Pooled it
- TMEM216 inhibits breast cancer lung metastasis by modulating IGF1R-IRS4 signaling pathway.Nature communications · 2026Article
- IRS4 is a PI3K-activating cancer dependency up-regulated through DNA rearrangements or epigenetic mechanisms in multiple solid tumors.Science advances · 2026Article
- Integrative Multiomic Classification Reveals Distinct Origins and Evolutionary Trajectories of Thymic Epithelial Tumors.Cancer research · 2026Article
- Article
- Efficient cellular transformation via protein delivery through the protrusion-derived extracellular vesicles.Nature communications · 2025Article
- Review
- AMPK phosphosite profiling by label-free mass spectrometry reveals a multitude of mTORC1-regulated substrates.npj metabolic health and disease · 2025Article
- PILRB potentiates the PI3K/AKT signaling pathway and reprograms cholesterol metabolism to drive gastric tumorigenesis and metastasis.Cell death & disease · 2024Article
- Enhancing Proteome Coverage by Using Strong Anion-Exchange in Tandem with Basic-pH Reversed-Phase Chromatography for Sample Multiplexing-Based Proteomics.Journal of proteome research · 2024Article
- Is Insulin Receptor Substrate4 (IRS4) a Platform Involved in the Activation of Several Oncogenes?Cancers · 2023Review
- Whole-exome sequencing and bioinformatic analyses revealed differences in gene mutation profiles in papillary thyroid cancer patients with and without benign thyroid goitre background.Frontiers in endocrinology · 2022Article
- Chronic venous disease patients show increased IRS-4 expression in the great saphenous vein wall.The Journal of international medical research · 2021Article
- Actinomycin D Arrests Cell Cycle of Hepatocellular Carcinoma Cell Lines and Induces p53-Dependent Cell Death: A Study of the Molecular Mechanism Involved in the Protective Effect of IRS-4.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Article
- Exendin-4 improves long-term potentiation and neuronal dendritic growth in vivo and in vitro obesity condition.Scientific reports · 2021Article
- Abnormal proinflammatory and stressor environmental with increased the regulatory cellular IGF-1/PAPP-A/STC and Wnt-1/β-Catenin canonical pathway in placenta of women with Chronic venous Disease during Pregnancy.International journal of medical sciences · 2021Observational
- Signal Transduction Pathways in Breast Cancer: The Important Role of PI3K/Akt/mTOR.Journal of oncology · 2020Review
- Robust network-based regularization and variable selection for high-dimensional genomic data in cancer prognosis.Genetic epidemiology · 2019Article
- Insulin receptor substrate-4 is overexpressed in colorectal cancer and promotes retinoblastoma-cyclin-dependent kinase activation.Journal of gastroenterology · 2018Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Insulin receptor substrate 1 (IRS1) and IRS2 are well-characterized adapter proteins that relay signals from receptor tyrosine kinases to downstream components of signalling pathways. In contrast, the function of IRS4 is not well understood. IRS4 overexpression has been associated with acute lymphoblastic leukaemia and subungual exostosis, while point mutations of IRS4 have been found in melanomas. Here, we show that while IRS4 expression is low in most cancer cell lines, IRS4 mRNA and protein levels are markedly elevated in certain cells including the NCI-H720, DMS114, HEK293T and HEK293AAV lines. Surprisingly, IRS4 expression was also strongly induced when HEK293 cells were infected with retroviral particles and selected under puromycin, making IRS4 expression a potential off-target effect of retroviral expression vectors. Cells with high expression of IRS4 displayed high phosphatidylinositol (3,4,5)-trisphosphate (PIP3) levels, as well as elevated Akt and p70 S6 kinase activities, even in the absence of growth factors. PI 3-kinase (PI3K) signalling in these cells depends on IRS4, even though these cells also express IRS1/2. Knockdown of IRS4 also inhibited cell proliferation in cells with high levels of IRS4. Together, these findings suggest IRS4 as a potential therapeutic target for cancers with high expression of this protein.
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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.