ArticleOncotarget2016
The anti-HER3 (ErbB3) therapeutic antibody 9F7-F11 induces HER3 ubiquitination and degradation in tumors through JNK1/2- dependent ITCH/AIP4 activation.
Article in Oncotarget, 2016. 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 19 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 24 citations in OpenAlex.
- miR-511-3p dysregulation-mediated AKT3/USP8 signaling imbalance: a molecular bridge between neuroinflammation and PSCI.Frontiers in immunology · 2026Article
- Deciphering USP8's pivotal role in cancer: mechanisms, clinical insights and contrasts with its function in pituitary adenomas.Journal of translational medicine · 2025Review
- Myofibrillogenesis Regulator-1 Regulates the Ubiquitin Lysosomal Pathway of Notch3 Intracellular Domain Through E3 Ubiquitin-Protein Ligase Itchy Homolog in the Metastasis of Non-Small Cell Lung Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Friend or foe? Reciprocal regulation between E3 ubiquitin ligases and deubiquitinases.Biochemical Society transactions · 2024Review
- UBE4B interacts with the ITCH E3 ubiquitin ligase to induce Ku70 and c-FLIPL polyubiquitination and enhanced neuroblastoma apoptosis.Cell death & disease · 2023Article
- Molecular basis of ubiquitin-specific protease 8 autoinhibition by the WW-like domain.Communications biology · 2021Article
- The E3 protein ubiquitin ligase Itch is a potential target in myeloid malignancies with marrow fibrosis.Translational cancer research · 2021Article
- Post-Translational Modifications That Drive Prostate Cancer Progression.Biomolecules · 2021Review
- The SPOP-ITCH Signaling Axis Protects Against Prostate Cancer Metastasis.Frontiers in oncology · 2021Article
- ITCH as a potential therapeutic target in human cancers.Seminars in cancer biology · 2020Review
- DUBs Activating the Hedgehog Signaling Pathway: A Promising Therapeutic Target in Cancer.Cancers · 2020Review
- ITCH-dependent proteasomal degradation of c-FLIP induced by the anti-HER3 antibody 9F7-F11 promotes DR5/caspase 8-mediated apoptosis of tumor cells.Cell communication and signaling : CCS · 2019Article
- Functional genomic characterization of a synthetic anti-HER3 antibody reveals a role for ubiquitination by RNF41 in the anti-proliferative response.The Journal of biological chemistry · 2019Article
- Estradiol promotes rapid degradation of HER3 in ER-positive breast cancer cell line MCF-7.Biochemistry and biophysics reports · 2018Article
- WW-Domain Containing Protein Roles in Breast Tumorigenesis.Frontiers in oncology · 2018Review
- A comprehensive review of heregulins, HER3, and HER4 as potential therapeutic targets in cancer.Oncotarget · 2017Review
- Article
- Upregulation of Circular RNA Itchy E3 Ubiquitin Protein Ligase Inhibits Cell Proliferation and Promotes Cell Apoptosis Through Targeting MiR-197 in Prostate Cancer.Technology in cancer research & treatmentArticle
- Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
Abstract
We characterized the mechanism of action of the neuregulin-non-competitive anti-HER3 therapeutic antibody 9F7-F11 that blocks the PI3K/AKT pathway, leading to cell cycle arrest and apoptosis in vitro and regression of pancreatic and breast cancer in vivo. We found that 9F7-F11 induces rapid HER3 down-regulation. Specifically, 9F7-F11-induced HER3 ubiquitination and degradation in pancreatic, breast and prostate cancer cell lines was driven mainly by the itchy E3 ubiquitin ligase (ITCH/AIP4). Overexpression of the ITCH/AIP4 inhibitor N4BP1 or small-interfering RNA-mediated knockdown of ITCH/AIP4 inhibited HER3 ubiquitination/degradation and PI3K/AKT signaling blockade induced by 9F7-F11. Moreover, 9F7-F11-mediated JNK1/2 phosphorylation led to ITCH/AIP4 activation and recruitment to HER3 for receptor ubiquitination and degradation. ITCH/AIP4 activity was activated by the deubiquitinases USP8 and USP9X, as demonstrated by RNA interference. Taken together, our results suggest that 9F7-F11-induced HER3 ubiquitination and degradation in cancer cells mainly occurs through JNK1/2-dependent ITCH/AIP4 activation.
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What OpenQuestion holds
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.