ArticleThe Journal of biological chemistry2010
Identification of a novel cell death receptor mediating IGFBP-3-induced anti-tumor effects in breast and prostate cancer.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 1 of them a synthesis that pooled it.
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Who cites it
79 citing papers in PubMed, 1 synthesis or guideline pooled it, 135 citations in OpenAlex.
- Does milk intake promote prostate cancer initiation or progression via effects on insulin-like growth factors (IGFs)? A systematic review and meta-analysis.Cancer causes & control : CCC · 2017Pooled it
- Synergistic cytotoxicity of recombinant IGFBP-3 and cisplatin in HPV18-positive HeLa cellsResearch in pharmaceutical sciences · 2026Article
- Endometriosis-related alterations in the endometrium revealed by integrated single-cell and AI-powered approaches.Nature communications · 2026Article
- Endometriosis at the Single-Cell Level: Molecular Insights and Implications for Assisted Reproduction Success.Biomolecules · 2026Review
- A multifaceted investigation into the impact of m6A methylation-related genes on pancreatic cancer, integrating insights from various databases and foundational experimental research.Annals of medicine and surgery (2012) · 2025Article
- Stage-specific role of IGFBP-3/TMEM219 pathway in liver fibrosis progression using a bile duct ligation rat model.Molecular biology reports · 2025Article
- IGFBP3 modulation of tumor pathogenesis and cell signaling pathways (Review).Oncology letters · 2025Review
- Promoting mucosal healing by targeting TMEM219-dependent intestinal epithelial stem cell defects in inflammatory bowel disease.The Journal of clinical investigation · 2025Article
- TMEM219 signaling promotes intestinal stem cell death and exacerbates colitis.The Journal of clinical investigation · 2025Article
- Role of IGFBP-3 in Human Diseases Relying on Different Cell Signaling Pathways.Advanced biomedical research · 2025Review
- The role of IGFBP-3 in tumor development and progression: enlightenment for diagnosis and treatment.Medical oncology (Northwood, London, England) · 2024Review
- Whole-exome sequencing of Nigerian benign prostatic hyperplasia reveals increased alterations in apoptotic pathways.The Prostate · 2024Article
- YKL-40 as a biomarker in various inflammatory diseases: A review.Biochemia medica · 2024Review
- Clinicopathological correlation of insulin-like growth factor binding protein 3 and their death receptor in patients with gastric cancer.Research in pharmaceutical sciences · 2024Article
- DRMref: comprehensive reference map of drug resistance mechanisms in human cancer.Nucleic acids research · 2024Article
- Aiming the magic bullet: targeted delivery of imaging and therapeutic agents to solid tumors by pHLIP peptides.Frontiers in pharmacology · 2024Review
- Understanding copy number variations through their genes: a molecular view on 16p11.2 deletion and duplication syndromes.Frontiers in pharmacology · 2024Review
- Expression of insulin-like growth factor binding protein-3 in HELLP syndrome.BMC pregnancy and childbirth · 2023Article
- Genes associated with inflammation for prognosis prediction for clear cell renal cell carcinoma: a multi-database analysis.Translational cancer research · 2023Article
- Signaling Pathways of the Insulin-like Growth Factor Binding Proteins.Endocrine reviews · 2023Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Insulin-like growth factor-binding protein-3 (IGFBP-3), a major regulator of endocrine actions of IGFs, is a p53-regulated potent apoptotic factor and is significantly suppressed in a variety of cancers. Recent epidemiologic studies suggest that IGFBP-3 contributes to cancer risk protection in a variety of cancers, and a polymorphic variation of IGFBP-3 influences cancer risk, although other studies vary in their conclusions. Some antiproliferative actions of IGFBP-3 have been reported to be independent of IGFs, but the precise biochemical/molecular mechanisms of IGF-independent, antiproliferative actions of IGFBP-3 are largely unknown. Here we report a new cell death receptor, IGFBP-3R, that is a single-span membrane protein and binds specifically to IGFBP-3 but not other IGFBP species. Expression analysis of IGFBP-3 and IGFBP-3R indicates that the IGFBP-3/IGFBP-3R axis is impaired in breast and prostate cancer. We also provide evidence for anti-tumor effect of IGFBP-3R in vivo using prostate and breast cancer xenografts in athymic nude mice. Further in vitro studies demonstrate that IGFBP-3R mediates IGFBP-3-induced caspase-8-dependent apoptosis in various cancer cells. Knockdown of IGFBP-3R attenuated IGFBP-3-induced caspase activities and apoptosis, whereas overexpression of IGFBP-3R enhanced IGFBP-3 biological effects. IGFBP-3R physically interacts and activates caspase-8, and knockdown of caspase-8 expression or activity inhibited IGFBP-3/IGFBP-3R-induced apoptosis. Here, we propose that IGFBP-3R represents a novel cell death receptor and is essential for the IGFBP-3-induced apoptosis and tumor suppression. Thus, the IGFBP-3/IGFBP-3R axis may provide therapeutic and prognostic value for the treatment of 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.