ArticleNature communications2021
Disruption of FOXO3a-miRNA feedback inhibition of IGF2/IGF-1R/IRS1 signaling confers Herceptin resistance in HER2-positive breast cancer.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 83 citations in OpenAlex.
- Engineered romidepsin biosynthetic pathways in Escherichia coli Nissle 1917 improve the efficacy of bacteria-mediated cancer therapy.PLoS biology · 2026Article
- Overcoming IGF1R-Mediated Resistance to Oncolytic HSV1 and Radiotherapy via Triple Combination Therapy.Research square · 2025Article
- SPP1 + macrophage and Treg interaction mediates immunosuppression and adverse survival in HER2 + breast cancer.Scientific reports · 2025Article
- The role of genetics and epigenetics in breast cancer: A comprehensive review of metastasis, risk factors, and future perspectives.Journal of pharmaceutical analysis · 2025Review
- BLID is a drug-responsive target of FOXO3a and multi-omics analysis reveals survival mechanisms and therapeutic vulnerabilities in BLID-deficient breast cancer cells.Oncology letters · 2025Article
- The mechanism of ncRNA in trastuzumab resistance in HER2-positive tumors.Medical oncology (Northwood, London, England) · 2025Review
- Recent Research Advances in HER2-Positive Breast Cancer Concerning Targeted Therapy Drugs.Molecules (Basel, Switzerland) · 2025Review
- Static training improves insulin resistance in skeletal muscle of type 2 diabetic mice via the IGF-2/IGF-1R pathway.Scientific reports · 2025Article
- The Role of the Fox Gene in Breast Cancer Progression.International journal of molecular sciences · 2025Review
- Genetic analysis reveals the shared genetic architecture between breast cancer and atrial fibrillation.Frontiers in genetics · 2025Article
- Adipose-derived exosomes ameliorate skeletal muscle atrophy via miR-146a-5p/IGF-1R signaling.Journal of nanobiotechnology · 2024Article
- The Biological Roles and Clinical Applications of the PI3K/AKT Pathway in Targeted Therapy Resistance in HER2-Positive Breast Cancer: A Comprehensive Review.International journal of molecular sciences · 2024Review
- Article
- Depicting Biomarkers for HER2-Inhibitor Resistance: Implication for Therapy in HER2-Positive Breast Cancer.Cancers · 2024Review
- Pyrotinib is effective in both trastuzumab-sensitive and primary resistant HER2-positive breast tumors.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024Article
- A Multifunctional Bimetallic Nanoplatform for Synergic Local Hyperthermia and Chemotherapy Targeting HER2-Positive Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Monkey multi-organ cell atlas exposed to estrogen.Life medicine · 2024Article
- The Transcriptional Landscape of Immune-Response 3'-UTR Alternative Polyadenylation in Melanoma.International journal of molecular sciences · 2024Article
- miRNAs as biomarkers of therapeutic response to HER2-targeted treatment in breast cancer: A systematic review.Biochemistry and biophysics reports · 2024Review
- Significant role ofBiochemistry and biophysics reports · 2024Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Resistance to Herceptin represents a significant challenge for successful treatment of HER2-positive breast cancer. Here, we show that in Herceptin-sensitive cells, FOXO3a regulates specific miRNAs to control IGF2 and IRS1 expression, retaining basic IGF2/IGF-1R/IRS1 signaling. The basic activity maintains expression of PPP3CB, a subunit of the serine/threonine-protein phosphatase 2B, to restrict FOXO3a phosphorylation (p-FOXO3a), inducing IGF2- and IRS1-targeting miRNAs. However, in Herceptin-resistant cells, p-FOXO3a levels are elevated due to transcriptional suppression of PPP3CB, disrupting the negative feedback inhibition loop formed by FOXO3a and the miRNAs, thereby upregulating IGF2 and IRS1. Moreover, we detect significantly increased IGF2 in blood and IRS1 in the tumors of breast cancer patients with poor response to Herceptin-containing regimens. Collectively, we demonstrate that the IGF2/IGF-1R/IRS1 signaling is aberrantly activated in Herceptin-resistant breast cancer via disruption of the FOXO3a-miRNA negative feedback inhibition. Such insights provide avenues to identify predictive biomarkers and effective strategies overcoming Herceptin resistance.
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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 Socratic graph.