ArticleMolecular and cellular biology2006
Suppression of insulin receptor substrate 1 (IRS-1) promotes mammary tumor metastasis.
Article in Molecular and cellular biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 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
48 citing papers in PubMed, 88 citations in OpenAlex.
- The Insulin Receptor Substrate 2 Mediates the Action of Insulin on HeLa Cell Migration via the PI3K/Akt Signaling Pathway.Current issues in molecular biology · 2023Article
- The insulin and IGF signaling pathway sustains breast cancer stem cells by IRS2/PI3K-mediated regulation of MYC.Cell reports · 2022Article
- Embryonic Programs in Cancer and Metastasis-Insights From the Mammary Gland.Frontiers in cell and developmental biology · 2022Review
- Epithelial-Mesenchymal Transition-Based Gene Signature and Distinct Molecular Subtypes for Predicting Clinical Outcomes in Breast Cancer.International journal of general medicine · 2022Article
- Diversity of insulin and IGF signaling in breast cancer: Implications for therapy.Molecular and cellular endocrinology · 2021Review
- Healthful aging mediated by inhibition of oxidative stress.Ageing research reviews · 2020Review
- Night-Shift Work Duration and Risk of Colorectal Cancer According toCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2020Article
- Glucocorticoid receptor-IRS-1 axis controls EMT and the metastasis of breast cancers.Journal of molecular cell biology · 2019Article
- Metabolomics Approach Based on Multivariate Techniques for Blood Transfusion Reactions.Scientific reports · 2019Article
- Insulin Receptor Substrate-1 (IRS-1) and IRS-2 expression levels are associated with prognosis in non-small cell lung cancer (NSCLC).PloS one · 2019Article
- Insulin Substrate Receptor (IRS) proteins in normal and malignant hematopoiesis.Clinics (Sao Paulo, Brazil) · 2018Review
- Association of IRS2 overexpression with disease progression in intrahepatic cholangiocarcinoma.Oncology letters · 2018Article
- Identification of a Novel Invasion-Promoting Region in Insulin Receptor Substrate 2.Molecular and cellular biology · 2018Article
- Integrated bioinformatics analysis reveals that the expression of cathepsin S is associated with lymph node metastasis and poor prognosis in papillary thyroid cancer.Oncology reports · 2018Article
- Article
- IRS-1 regulates proliferation, invasion and metastasis of pancreatic cancer cells through MAPK and PI3K signaling pathways.International journal of clinical and experimental pathology · 2018Article
- IL-4 and IL-13 Receptor Signaling From 4PS to Insulin Receptor Substrate 2: There and Back Again, a Historical View.Frontiers in immunology · 2018Review
- Differential involvement of the microtubule cytoskeleton in insulin receptor substrate 1 (IRS-1) and IRS-2 signaling to AKT determines the response to microtubule disruption in breast carcinoma cells.The Journal of biological chemistry · 2017Article
- Insulin Receptor Substrate Adaptor Proteins Mediate Prognostic Gene Expression Profiles in Breast Cancer.PloS one · 2016Article
- 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
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
The insulin receptor substrate (IRS) proteins are cytoplasmic adaptors that organize signaling complexes downstream of activated cell surface receptors. Here, we show that IRS-1 and IRS-2, despite significant homology, play critical yet distinct functions in breast cancer, and we identify specific signaling pathways that are influenced by IRS-1 using the polyoma virus middle-T (PyV-MT) transgenic mouse model of mammary carcinoma and Irs-1 null (Irs1(-/-)) mice. The absence of Irs-1 expression enhanced metastatic spread significantly without a significant effect on primary tumor growth. Orthotopic transplant studies revealed that the increased metastatic potential of Irs1-deficient tumor cells is cell autonomous. Mammary tumors that developed in PyV-MT::Irs1(-/-) mice exhibited elevated Irs-2 function and enhanced phosphatidylinositol 3-kinase/Akt/mTor activity, suggesting that one mechanism by which Irs-1 impedes metastasis is to suppress Irs-2-dependent signaling. In support of this mechanism, reduction of Irs-2 expression in Irs1(-/-) tumor cells restored mTor signaling to wild-type levels. PyV-MT::Irs1(-/-) tumors also exhibited a significant increase in vascular endothelial growth factor expression and microvessel density, which could facilitate their dissemination. The significance of our findings for human breast cancer is heightened by our observation that Irs-1 is inactivated in wild-type, metastatic mammary tumors by serine phosphorylation. Collectively, our findings reveal that inactivation of IRS-1 enhances breast cancer metastasis and support the novel hypothesis that IRS-1 has metastasis suppressor functions for breast cancer.
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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.