ArticleThe Journal of biological chemistry2014
Insulin receptor substrate 1/2 (IRS1/2) regulates Wnt/β-catenin signaling through blocking autophagic degradation of dishevelled2.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 64 citations in OpenAlex.
- Therapeutic delivery of albumin-binding siRNA targeting IRS2 to diverse cell types reduces mammary tumor growth.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Small Extracellular Vesicles in Gestational Diabetes Mellitus: Current Landscape and Emerging Diagnostic Horizons.Journal of extracellular biology · 2026Review
- Single-cell transcriptomics showed that maternal polychlorinated biphenyl exposure dysregulated cell type-specific metabolic responses in the livers of female mouse offsprings.Drug metabolism and disposition: the biological fate of chemicals · 2026Article
- Wnt/β-Catenin-mTOR-autophagy crosstalk in breast cancer: context-dependent control of tumor progression, immune suppression, and therapeutic resistance.Frontiers in immunology · 2026Review
- Impaired WNT3/IGF-1 Signaling in Dorsal Dentate Gyrus Contributes to Chronic Pain-Related Cognitive Impairment.CNS neuroscience & therapeutics · 2025Article
- Gene expression changes in pancreatic α-cell lines following knock-out Of either CK2α or CK2α'.Biological research · 2025Article
- Cross-Talk between NOK and EGFR: Juxtamembrane and Kinase domain interactions enhancing STAT3/5 signaling in breast cancer tumorigenesis.Translational oncology · 2025Article
- First Trimester Placental Biomarkers for Pregnancy Outcomes.International journal of molecular sciences · 2024Review
- MicroRNAs Associated with the Pathophysiological Mechanisms of Gestational Diabetes Mellitus: A Systematic Review for Building a Panel of miRNAs.Journal of personalized medicine · 2023Review
- Exploring the potential of microRNA as a diagnostic tool for gestational diabetes.Journal of translational medicine · 2023Review
- The impact of aging and oxidative stress in metabolic and nervous system disorders: programmed cell death and molecular signal transduction crosstalk.Frontiers in immunology · 2023Review
- Prospecting of exosomal-miRNA signatures as prognostic marker for gestational diabetes mellitus and other adverse pregnancy outcomes.Frontiers in endocrinology · 2023Review
- Dysregulation of Wnt signaling in bone of type 2 diabetes mellitus and diabetic Charcot arthropathy.BMC musculoskeletal disorders · 2022Article
- The implications of exosomes in pregnancy: emerging as new diagnostic markers and therapeutics targets.Cell communication and signaling : CCS · 2022Review
- The Mystery of Exosomes in Gestational Diabetes Mellitus.Oxidative medicine and cellular longevity · 2022Review
- miRNAs as Predictive Factors in Early Diagnosis of Gestational Diabetes Mellitus.Frontiers in endocrinology · 2022Article
- Review
- Inhibition of Dishevelled-2 suppresses the biological behavior of pancreatic cancer by downregulating Wnt/β-catenin signaling.Oncology letters · 2021Article
- Insulin receptor substrate-1 and dishevelled 2 are negatively regulated by microRNA-144 and inhibit nasopharyngeal carcinoma cell malignancy.Experimental and therapeutic medicine · 2021Article
- Sequestosome 1/p62: A multitasker in the regulation of malignant tumor aggression (Review).International journal of oncology · 2021Review
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Wnt signaling plays a pivotal role in cell proliferation, tissue homeostasis, and tumorigenesis. Dishevelled (Dvl) is a central node of Wnt signaling. Insulin receptor substrates (IRSs), as a critical component of insulin signaling, are involved in cell proliferation, metabolism, and cancer development. In this study, we report that IRS1/2 promotes Wnt/β-catenin signaling by stabilizing Dvl2. We found that IRS1/2 interacts with Dvl2. Overexpression of IRS1/2 increased the protein level of Dvl2 and promoted canonical Wnt signaling, as evidenced by the increased T cell-specific factor 4 transcriptional activity and the up-regulation of expression of CYCLIN D1 and c-MYC, two Wnt target genes critical for cell growth, whereas depletion of IRS1/2 reduced the level of Dvl2 and attenuated Wnt/β-catenin signaling. Biochemical analyses revealed that IRS1/2 decreased Lys-63-linked ubiquitination of Dvl2 and stabilized Dvl2 protein via suppressing its autophagy-mediated degradation. We further revealed that IRS1/2 blocks autophagy-induced formation of the Dvl2-p62/SQSTM1 complex, resulting in disabled association of Dvl2 to autophagosomes. We demonstrated that IRS1/2 promoted the induction of epithelial-mesenchymal transition (EMT) and cell proliferation in response to Wnt stimulation, whereas depletion of Dvl2 impaired the IRS1/2-mediated EMT and cell growth. Our findings revealed that IRS1/2 promotes EMT and cell proliferation through stabilizing Dvl2.
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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.