ArticleNature communications2023
Epigenetic regulation of Neuregulin 1 promotes breast cancer progression associated to hyperglycemia.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 18 citations in OpenAlex.
- Neural regulation of cancer: from microenvironmental hijacking to systemic circuit co-option.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- From diabetes to tumor growth: unravelling the impact of glucose-lowering therapies.Endocrine · 2026Review
- Hypoxia and HIF signalling in tumour microenvironment: linking immune evasion, metabolic rewiring and epigenetic regulation.Expert reviews in molecular medicine · 2026Review
- Unraveling Diabetes Mellitus-Driven Tumorigenesis: From Pathophysiological Mechanisms, Therapeutic Drugs to Tailor-Made Nanosystems.International journal of nanomedicine · 2026Review
- Anti-diabetic medications and cancer: links beyond glycemic and body weight control.Precision clinical medicine · 2025Review
- In-depth analysis of the tear fluid glycoproteome reveals diverse lacritin glycosylation and spliceoforms.The Journal of biological chemistry · 2025Article
- In-depth analysis of the tear fluid glycoproteome reveals diverse lacritin glycosylation and spliceoforms.bioRxiv : the preprint server for biology · 2025Article
- Elevated neuregulin‑1 expression modulates tumor malignancy and autophagy in esophageal squamous cell carcinoma.International journal of molecular medicine · 2025Article
- Vitamin D ameliorates prediabetic cardiac injure via modulation of the ErbB4/ferroptosis signaling axis.Frontiers in immunology · 2025Article
- Long-read sequencing of an advanced cancer cohort resolves rearrangements, unravels haplotypes, and reveals methylation landscapes.Cell genomics · 2024Article
- Influence of Type 2 Diabetes and Adipose Tissue Dysfunction on Breast Cancer and Potential Benefits from Nutraceuticals Inducible in Microalgae.Nutrients · 2024Review
- Metabolic memory: mechanisms and diseases.Signal transduction and targeted therapy · 2024Review
- How early life respiratory viral infections impact airway epithelial development and may lead to asthma.Frontiers in pediatrics · 2024Review
- Diabetes and Cancer: A Twisted Bond.Oncology reviews · 2024Review
- Modulation of Notch Signaling by Small-Molecular Compounds and Its Potential in Anticancer Studies.Cancers · 2023Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hyperglycemia is a risk factor for breast cancer-related morbidity and mortality. Hyperglycemia induces Neuregulin 1 (Nrg1) overexpression in breast cancer, which subsequently promotes tumor progression. However, molecular mechanisms underlying hyperglycemia-induced Nrg1 overexpression remain poorly understood. Here, we show that hyperglycemia causes active histone modifications at the Nrg1 enhancer, forming enhanceosome complexes where recombination signal binding protein for immunoglobulin kappa J region (RBPJ), E1A binding protein p300 (P300), and SET domain containing 1 A (SETD1A) are recruited to upregulate Nrg1 expression. Deletions in RBPJ-binding sites causes hyperglycemia-controlled Nrg1 levels to be downregulated, resulting in decreased tumor growth in vitro and in vivo. Mice with modest-temporary hyperglycemia, induced by low-dose short-exposure streptozotocin, display accelerated tumor growth and lapatinib resistance, whereas combining lapatinib with N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S42 phenylglycine t-butyl ester (DAPT) ameliorates tumor growth under these modest hyperglycemic conditions by inhibiting NOTCH and EGFR superfamilies. NOTCH activity is correlated with NRG1 levels, and high NRG1 levels predicts poor outcomes, particularly in HER2-positive breast cancer patients. Our findings highlight the hyperglycemia-linked epigenetic modulation of NRG1 as a potential therapeutic strategy for treating breast cancer patients with diabetes.
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