ArticleJournal of gastroenterology2018
Insulin receptor substrate-4 is overexpressed in colorectal cancer and promotes retinoblastoma-cyclin-dependent kinase activation.
Article in Journal of gastroenterology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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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
14 citing papers in PubMed, 17 citations in OpenAlex.
- 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
- Is Insulin Receptor Substrate4 (IRS4) a Platform Involved in the Activation of Several Oncogenes?Cancers · 2023Review
- The Influence of Race/Ethnicity on the Transcriptomic Landscape of Uterine Fibroids.International journal of molecular sciences · 2023Article
- Patients with Invasive Lobular Carcinoma Show a Significant Increase in IRS-4 Expression Compared to Infiltrative Ductal Carcinoma-A Histopathological Study.Medicina (Kaunas, Lithuania) · 2022Article
- Prognostic role of IRS-4 in the survival of patients with pancreatic cancer.Histology and histopathology · 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
- An Update on the Potential Roles of E2F Family Members in Colorectal Cancer.Cancer management and research · 2021Review
- A comprehensive review of the roles of E2F1 in colon cancer.American journal of cancer research · 2020Review
- Sub-lethal Doses of Polybrominated Diphenyl Ethers, in Vitro, Promote Oxidative Stress and Modulate Molecular Markers Related to Cell Cycle, Antioxidant Balance and Cellular Energy Management.International journal of environmental research and public health · 2019Article
- Overexpression of IRS-4 Correlates with Procaspase 3 Levels in Tumoural Tissue of Patients with Colorectal Cancer.Journal of oncology · 2018Article
- hsa_circ_0023409 Accelerates Gastric Cancer Cell Growth and Metastasis Through Regulating the IRS4/PI3K/AKT Pathway.Cell transplantationArticle
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundInsulin receptor substrate 4 (IRS-4) is an adaptor protein for which new evidence suggests plays a role in tumour promotion.
methodsWe described nuclear IRS-4 in RKO colon cancer cell lines in biopsies of patients with colorectal cancer (CRC) (n = 20) and in matched adjacent normal colorectal (MANC) tissue (n = 20).
resultsTreatment with physiological doses of IGF-1 promoted nuclear influx of IRS-4 from cellular cytosol in RKO cells. When exogenous IRS-4 was overexpressed in RKO cells, there was an increase in cyclin D1, cyclin E, E2F1, pRB Ser 809/811 and pRB Ser 705 levels compared with the empty vector-transfected cells. Some of these changes returned to control values after wortmannin treatment. Subcellular fractionation showed an overexpression of IRS-4 in the cytoplasm, membrane, and nuclei of tumour samples, whereas the levels of the protein were barely detectable in the three compartments of normal samples. Immunohistochemical studies showed positive nuclear IRS-4 staining in over 74% of the tumour cells. IRS-4 was strongly overexpressed in tumoural tissues from CRC patients compared to MANC tissues. The up-regulation of IRS-4 in CRC samples correlated significantly with the increase of several G1 checkpoint proteins including cyclin D1 (r = 0.6662), Rb (r = 0.7779), pRb Serine 809/811 (r = 0.6864), pRb serine 705 (r = 0.6261) and E2F1 (r = 0.8702).
conclusionsTaken together, our findings suggest that IRS-4 promotes retinoblastoma-cyclin-dependent kinase activation and it may serve as a pharmacological target since its expression is very low in normal tissue, including colonic epithelium.
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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.