ArticleNeoplasia (New York, N.Y.)2011
Regulation of EGFR protein stability by the HECT-type ubiquitin ligase SMURF2.
Article in Neoplasia (New York, N.Y.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 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
41 citing papers in PubMed, 52 citations in OpenAlex.
- GSTT2 Switches from a Homeostatic Antioxidant to a Cell-Cycle-Coupled Factor in Therapy-Resistant Esophageal Adenocarcinoma.Cancers · 2026Article
- ISGylation of γH2AX retains MDC1 and facilitates homologous recombination repair causing radioresistance in esophageal adenocarcinoma.The Journal of biological chemistry · 2026Article
- SMURF2 in Anticancer Therapy: Dual Role in Carcinogenesis and Theranostics.International journal of molecular sciences · 2026Review
- Smurf2 enhances ubiquitin-mediated degradation of CASC3 and attenuates leukemia progression.iScience · 2025Article
- SMURF2 Facilitates GAP17 Isoform 1 Membrane Displacement to Promote Mutant p53-KRAS Oncogenic Synergy.Molecular cancer research : MCR · 2025Article
- Epsin3 promotes non-small cell lung cancer progression via modulating EGFR stability.Cell & bioscience · 2025Article
- GRAIL1 Stabilizes Misfolded Mutant p53 through a Ubiquitin Ligase-Independent, Chaperone Regulatory Function.Molecular cancer research : MCR · 2024Article
- ISG15/GRAIL1/CD3 axis influences survival of patients with esophageal adenocarcinoma.JCI insight · 2024Article
- Isoform alterations in the ubiquitination machinery impacting gastrointestinal malignancies.Cell death & disease · 2024Review
- JMJD5 inhibits lung cancer progression by facilitating EGFR proteasomal degradation.Cell death & disease · 2023Article
- Budding uninhibited by benzimidazoles-1 (BUB1) regulates EGFR signaling by reducing EGFR internalization.Aging · 2023Article
- PELI1 and EGFR cooperate to promote breast cancer metastasis.Oncogenesis · 2023Article
- TRAF4 hyperactivates HER2 signaling and contributes to Trastuzumab resistance in HER2-positive breast cancer.Oncogene · 2022Article
- UBCH5 Family Members Differentially Impact Stabilization of Mutant p53 via RNF128 Iso1 During Barrett's Progression to Esophageal Adenocarcinoma.Cellular and molecular gastroenterology and hepatology · 2022Article
- SMAD-specific E3 ubiquitin ligase 2 promotes angiogenesis by facilitating PTX3 degradation in MSCs from patients with ankylosing spondylitis.Stem cells (Dayton, Ohio) · 2021Article
- Ubiquitin ligase SMURF2 enhances epidermal growth factor receptor stability and tyrosine-kinase inhibitor resistance.The Journal of biological chemistry · 2020Article
- TRIB3-EGFR interaction promotes lung cancer progression and defines a therapeutic target.Nature communications · 2020Article
- SMURF2 prevents detrimental changes to chromatin, protecting human dermal fibroblasts from chromosomal instability and tumorigenesis.Oncogene · 2020Article
- Isoforms of RNF128 Regulate the Stability of Mutant P53 in Barrett's Esophageal Cells.Gastroenterology · 2020Article
- Role of Ubiquitination in PTEN Cellular Homeostasis and Its Implications in GB Drug Resistance.Frontiers in oncology · 2020Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Epidermal growth factor receptor (EGFR) is overexpressed in a variety of epithelial tumors and is considered to be an important therapeutic target. Although gene amplification is responsible for EGFR overexpression in certain human malignancies including lung and head and neck cancers, additional molecular mechanisms are likely. Here, we report a novel interaction of EGFR with an HECT-type ubiquitin ligase SMURF2, which can ubiquitinate, but stabilize EGFR by protecting it from c-Cbl-mediated degradation. Conversely, small interfering RNA (siRNA)-mediated knockdown of SMURF2 destabilized EGFR, induced an autophagic response and reduced the clonogenic survival of EGFR-expressing cancer cell lines, with minimal effects on EGFR-negative cancer cells, normal fibroblasts, and normal epithelial cells. UMSCC74B head and neck squamous cancer cells, which form aggressive tumors in nude mice, significantly lost in vivo tumor-forming ability on siRNA-mediated SMURF2 knockdown. Gene expression microarray data from 443 lung adenocarcinoma patients, and tissue microarray data from 67 such patients, showed a strong correlation of expression between EGFR and SMURF2 at the messenger RNA and protein levels, respectively. Our findings suggest that SMURF2-mediated protective ubiquitination of EGFR may be responsible for EGFR overexpression in certain tumors and support targeting SMURF2-EGFR interaction as a novel therapeutic approach in treating EGFR-addicted tumors.
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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.