ArticleOncogene2007
Role of epidermal growth factor receptor degradation in gemcitabine-mediated cytotoxicity.
Article in Oncogene, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. 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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
35 citing papers in PubMed, 71 citations in OpenAlex.
- Systems Pharmacodynamic Model of Combined Gemcitabine and Trabectedin in Pancreatic Cancer Cells. Part I: Effects on Signal Transduction Pathways Related to Tumor GrowthJournal of pharmaceutical sciences · 2024Article
- Akt kinase LANCL2 functions as a key driver in EGFR-mutant lung adenocarcinoma tumorigenesis.Cell death & disease · 2021Article
- Non-metabolic role of UCK2 links EGFR-AKT pathway activation to metastasis enhancement in hepatocellular carcinoma.Oncogenesis · 2020Article
- Ubiquitin ligase SMURF2 enhances epidermal growth factor receptor stability and tyrosine-kinase inhibitor resistance.The Journal of biological chemistry · 2020Article
- Local Delivery of Gemcitabine Inhibits Pancreatic and Cholangiocarcinoma Tumor Growth by Promoting Epidermal Growth Factor Receptor Degradation.International journal of molecular sciences · 2020Article
- GLRX inhibition enhances the effects of geftinib in EGFR-TKI-resistant NSCLC cells through FoxM1 signaling pathway.Journal of cancer research and clinical oncology · 2019Article
- Glycerol kinase 5 confers gefitinib resistance through SREBP1/SCD1 signaling pathway.Journal of experimental & clinical cancer research : CR · 2019Article
- Depicting Changes in Tumor Biology in Response to Cetuximab Monotherapy or Combination Therapy by Apoptosis and Proliferation Imaging UsingJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2018Article
- Protease-activated receptor 1 inhibits cholesterol efflux and promotes atherogenesis via cullin 3-mediated degradation of the ABCA1 transporter.The Journal of biological chemistry · 2018Article
- ST6Gal-I sialyltransferase promotes chemoresistance in pancreatic ductal adenocarcinoma by abrogating gemcitabine-mediated DNA damage.The Journal of biological chemistry · 2018Article
- Differential protein stability of EGFR mutants determines responsiveness to tyrosine kinase inhibitors.Oncotarget · 2016Article
- Low expression of the E3 ubiquitin ligase CBL confers chemoresistance in human pancreatic cancer and is targeted by epidermal growth factor receptor inhibition.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015Article
- Dual inhibition of EGFR at protein and activity level via combinatorial blocking of PI4KIIα as anti-tumor strategy.Protein & cell · 2014Article
- KRAS protein stability is regulated through SMURF2: UBCH5 complex-mediated β-TrCP1 degradation.Neoplasia (New York, N.Y.) · 2014Article
- Efficacy of an EGFR-specific peptide against EGFR-dependent cancer cell lines and tumor xenografts.Neoplasia (New York, N.Y.) · 2014Article
- Effect of erlotinib on epidermal growth factor receptor and downstream signaling in oral cavity squamous cell carcinoma.Head & neck · 2013Article
- Efficacy of gemcitabine and cetuximab combination treatment in head and neck squamous cell carcinoma.Molecular and clinical oncology · 2013Article
- Wild-type EGFR is stabilized by direct interaction with HSP90 in cancer cells and tumors.Neoplasia (New York, N.Y.) · 2012Article
- Cisplatin and ultra-violet-C synergistically down-regulate receptor tyrosine kinases in human colorectal cancer cells.Molecular cancer · 2012Article
- Degradation of epidermal growth factor receptor mediates dasatinib-induced apoptosis in head and neck squamous cell carcinoma cells.Neoplasia (New York, N.Y.) · 2012Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
We have recently reported that treatment with gemcitabine, a potent chemotherapeutic agent and radiation sensitizer, stimulates phosphorylation of the epidermal growth factor receptor (EGFR). Because phosphorylation of EGFR is known to precede receptor degradation, we hypothesized that gemcitabine treatment may also result in EGFR degradation. In two human head and neck cancer cell lines, UMSCC-1 and UMSCC-6, we demonstrated an approximately 80% decrease in total EGFR levels at 72 h after a 2-h treatment with 1 muM gemcitabine. Neither cisplatin nor 5-fluorouracil, which are used to treat head and neck cancer, caused EGFR degradation. EGFR downregulation did not occur at the level of transcription, as assessed by reverse transcription-polymerase chain reaction (RT-PCR), but instead occurred via phosphorylation and ubiquitination of the receptor along a proteosome/lysosome-mediated pathway. Inhibition of EGFR degradation, by either pretreatment with the EGFR tyrosine kinase inhibitor gefitinib or by exposure to the proteosome/lysosome inhibitor MG132, significantly reduced gemcitabine-induced cell death. These results suggest that EGFR degradation may be a novel mechanism for gemcitabine-mediated cell death. These findings also indicate that caution should be exercised when combining gemcitabine with agents that may prevent EGFR degradation, such as EGFR tyrosine kinase inhibitors administered in a suboptimal sequence or proteosome inhibitors.
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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.