ArticleOncogene2014
The role of insulin-like growth factor binding protein-3 in the breast cancer cell response to DNA-damaging agents.
Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 69 citations in OpenAlex.
- Insulin-like growth factor 1 receptor expression and IGF1R 3129G > T polymorphism are associated with response to neoadjuvant chemotherapy in breast cancer patients: results from the NEOZOTAC trial (BOOG 2010-01).Breast cancer research : BCR · 2016Trial
- Synergistic cytotoxicity of recombinant IGFBP-3 and cisplatin in HPV18-positive HeLa cellsResearch in pharmaceutical sciences · 2026Article
- MAVS as a Key Regulator of Tumor Proliferation, Survival, the Tumor Microenvironment, and Immunity.Biomolecules · 2026Article
- The mechanism of high mobility group box-1 in the proliferation and macrophage polarization in esophageal squamous cell carcinoma cells.European journal of medical research · 2025Article
- The human-specific noncoding RNAFASEB bioAdvances · 2025Article
- Hypoxia-Induced Histone Lactylation Drives Cisplatin Resistance in Bladder Cancer by Promoting RBM15-Dependent mResearch (Washington, D.C.) · 2025Article
- The Role of Insulin-like Growth Factor Binding Protein (IGFBP)-2 in DNA Repair and Chemoresistance in Breast Cancer Cells.Cancers · 2024Article
- IGFBP3 promotes resistance to Olaparib via modulating EGFR signaling in advanced prostate cancer.iScience · 2024Article
- Signaling Pathways of the Insulin-like Growth Factor Binding Proteins.Endocrine reviews · 2023Article
- Integrative transcriptomics and cell systems analyses reveal protective pathways controlled by Igfbp-3 in anthracycline-induced cardiotoxicity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- IGFBP3 induced by the TGF-β/EGFRvIII transactivation contributes to the malignant phenotype of glioblastoma.iScience · 2023Article
- ThroughoutFrontiers in endocrinology · 2023Article
- Article
- Roles of IGFBP-3 in cell migration and growth in an endophytic tongue squamous cell carcinoma cell line.Scientific reports · 2022Article
- Review
- IGFBP-3 functions as a molecular switch that mediates mitochondrial and metabolic homeostasis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- RNA binding proteins in osteoarthritis.Frontiers in cell and developmental biology · 2022Review
- Targeted and systemic insights into the crosstalk between DNA-dependent protein kinase catalytic subunit and receptors of estrogen, progesterone and epidermal growth factor in the context of cancer.Molecular biology reports · 2022Review
- Review
- The evolving complexity of DNA damage foci: RNA, condensates and chromatin in DNA double-strand break repair.DNA repair · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Following exposure to radiation and chemotherapeutic agents, the epidermal growth factor receptor (EGFR) can modulate the repair of DNA double-strand breaks (DSB) by forming protein complexes that include the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs). This is one of the key mechanism by which tumors become resistant to DNA-damaging therapies. Our previous studies have shown that insulin-like growth factor binding protein-3 (IGFBP-3) is a substrate for DNA-PKcs, and can transactivate EGFR. We therefore questioned whether IGFBP-3 might interact with the EGFR-DNA-PK complex that regulates the DNA damage response. The aim of this study was to delineate the role of IGFBP-3 in the response of breast cancer cells to DSB-inducing chemotherapeutic agents. In the estrogen receptor-negative breast cancer cell lines MDA-MB-468 and Hs578T, which express IGFBP-3 highly, nuclear localization of EGFR and IGFBP-3 was enhanced by treatment with cytotoxic drugs etoposide or doxorubicin and reduced by the EGFR kinase inhibitor gefitinib. Enhanced association among IGFBP-3, EGFR and DNA-PKcs, following the exposure to DNA-damaging drugs was supported by both co-immunoprecipitation analysis and direct visualization by proximity ligation assay. The activation of DNA-PKcs at Ser2056, DNA repair as measured by a nonhomologous end-joining assay, and the increase in EGFR and DNA-PKcs interaction induced by DNA-damaging agents, were all decreased by IGFBP-3 silencing, suggesting that IGFBP-3 has an obligatory role in the DNA repair response to DNA-damaging therapy. In conclusion, IGFBP-3 co-translocation to the nucleus of breast cancer cells and its formation of a complex with DNA-PKcs and EGFR in response to DNA damage shows its potential involvement in the regulation of DNA repair. This suggests the possibility of a therapeutic approach for sensitizing breast cancer to chemo- or radiotherapy by targeting the DNA repair function of IGFBP-3.
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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.