ArticleOncogene2008
Picropodophyllin induces downregulation of the insulin-like growth factor 1 receptor: potential mechanistic involvement of Mdm2 and beta-arrestin1.
Article in Oncogene, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 35 papers.
What it found
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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
35 citing papers in PubMed.
- An inherent T cell-activating mRNA delivery carrier for in vivo CAR T generation.Nature materials · 2026Article
- Galectin and Myc enable cochlear progenitor expansion in vitro and in vivo.bioRxiv : the preprint server for biology · 2026Article
- Insulin and Insulin-like Growth Factor 1 Signaling as a Modulator of MYC Expression in the Meibomian Gland.Biomedicines · 2026Article
- Contrasting consequences of podocyte insulin-like growth factor 1 receptor inhibition.iScience · 2024Article
- Mini Review: Molecular Interpretation of the IGF/IGF-1R Axis in Cancer Treatment and Stem Cells-Based Therapy in Regenerative Medicine.International journal of molecular sciences · 2022Review
- Recent developments in the structural characterisation of the IR and IGF1R: implications for the design of IR-IGF1R hybrid receptor modulators.RSC medicinal chemistry · 2022Review
- IGF-1R is a molecular determinant for response to p53 reactivation therapy in conjunctival melanoma.Oncogene · 2022Article
- Podophyllotoxin: History, Recent Advances and Future Prospects.Biomolecules · 2021Review
- Disrupting Insulin and IGF Receptor Function in Cancer.International journal of molecular sciences · 2021Review
- Article
- Regulation of Hippo-YAP signaling by insulin-like growth factor-1 receptor in the tumorigenesis of diffuse large B-cell lymphoma.Journal of hematology & oncology · 2020Article
- IGF-1R Inhibitor Ameliorates Neuroinflammation in an Alzheimer's Disease Transgenic Mouse Model.Frontiers in cellular neuroscience · 2020Article
- Review
- Personalized Medicine in Malignant Melanoma: Towards Patient Tailored Treatment.Frontiers in oncology · 2018Review
- Enhanced response of melanoma cells to MEK inhibitors following unbiased IGF-1R down-regulation.Oncotarget · 2017Article
- Insulin Growth Factor 1 Protects Neural Stem Cells Against Apoptosis Induced by Hypoxia Through Akt/Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase (Akt/MAPK/ERK) Pathway in Hypoxia-Ishchemic Encephalopathy.Medical science monitor : international medical journal of experimental and clinical research · 2017Article
- Deciphering Brain Insulin Receptor and Insulin-Like Growth Factor 1 Receptor Signalling.Journal of neuroendocrinology · 2016Article
- Insulin-like growth factor system in cancer: novel targeted therapies.BioMed research international · 2015Review
- The association of TP53 mutations with the resistance of colorectal carcinoma to the insulin-like growth factor-1 receptor inhibitor picropodophyllin.BMC cancer · 2013Article
- MiR-223 deficiency increases eosinophil progenitor proliferation.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The insulin-like growth factor 1 receptor (IGF-1R) is crucial for growth and survival of malignant cells. Experience in targeting IGF-1R in cancer models has shown that strategies promoting downregulation of the receptor are much more efficient in inducing apoptosis than those inhibiting the IGF-1R activity. Recently, we found that the cyclolignan picropodophyllin (PPP) inhibits phosphorylation of IGF-1R and activation of downstream signaling without interfering with the highly homologous insulin receptor (IR). Furthermore, PPP treatment caused strong regression of tumor grafts and prolonged survival of animals with systemic tumor disease. Here we demonstrate that PPP also downregulates the IGF-1R, whereas the IR and several other receptors were not affected. PPP-induced IGF-1R downregulation required expression of the MDM2 E3 ligase, which recently was found to ubiquitinate and cause degradation of the IGF-1R. In addition knockdown of beta-arrestin1, the adaptor molecule known to bridges MDM2 and IGF-1R, prevented downregulation of the receptor and significantly decreased PPP-induced cell death. All together these data suggest that PPP downregulates IGF-1R by interfering with the action of beta-arrestin1/MDM2 as well as the achieved receptor downregulation contributes to the apoptotic effect of PPP.
Indexed as
Identifiers
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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.