ArticleEBioMedicine2020
Systematic identification of CDC34 that functions to stabilize EGFR and promote lung carcinogenesis.
Article in EBioMedicine, 2020. 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 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
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- A novel ubiquitination-based molecular signature predicts prognosis in diffuse large B-cell lymphoma.Annals of hematology · 2025Article
- Proteomic Analysis Uncovers Enhanced Inflammatory Phenotype and Distinct Metabolic Changes in IDH1 Mutant Glioma Cells.International journal of molecular sciences · 2025Article
- Abnormally High Expression of DNAJB6 Accelerates Malignant Progression of Lung Adenocarcinoma.Biomedicines · 2024Article
- Advances of E3 ligases in lung cancer.Biochemistry and biophysics reports · 2024Review
- SERPINE2 promotes liver cancer metastasis by inhibiting c-Cbl-mediated EGFR ubiquitination and degradation.Cancer communications (London, England) · 2024Article
- LGR4 attenuates MGP expression and suppresses EGFR activation-induced triple-negative breast cancer metastasis.American journal of cancer research · 2024Article
- The role of CBL family ubiquitin ligases in cancer progression and therapeutic strategies.Frontiers in pharmacology · 2024Review
- Function, mechanism and drug discovery of ubiquitin and ubiquitin-like modification with multiomics profiling for cancer therapy.Acta pharmaceutica Sinica. B · 2023Review
- Discovery of potential biomarkers for lung cancer classification based on human proteome microarrays using Stochastic Gradient Boosting approach.Journal of cancer research and clinical oncology · 2023Article
- Immune cell-specific smoking-related expression characteristics are revealed by re-analysis of transcriptomes from the CEDAR cohort.Central-European journal of immunology · 2022Article
- Pharmacological Modulation of Ubiquitin-Proteasome Pathways in Oncogenic Signaling.International journal of molecular sciences · 2021Review
- Ubiquitin-Conjugating Enzymes in Cancer.Cells · 2021Review
- The Molecular Basis of Ubiquitin-Conjugating Enzymes (E2s) as a Potential Target for Cancer Therapy.International journal of molecular sciences · 2021Review
- Integrated Analysis of miRNA-mRNA Regulatory Networks Associated with Osteonecrosis of the Femoral Head.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Targeting CDC34 E2 ubiquitin conjugating enzyme for lung cancer therapy.EBioMedicine · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
21 authors at 8 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHow the oncoprotein epidermal growth factor receptor (EGFR) evades proteolytic degradation and accumulates in non-small cell lung cancer (NSCLC) remains unclear, and ubiquitin pathway genes (UPGs) that are critical to NSCLC needs to be systematically identified.
methodsA total of 696 UPGs (including E1, E2, E3, and deubiquitinases) were silenced by small interfering RNA (siRNA) library in NSCLC cells, the candidates were verified, and their significance was evaluated in patients with NSCLC. The effects of a candidate gene on EGFR were investigated in vitro and in vivo.
findingsWe report 31 candidates that are required for cell proliferation, with the E2 ubiquitin conjugase CDC34 as the most significant one. CDC34 is elevated in tumor tissues in 76 of 114 (66.7%) NSCLCs and inversely associated with prognosis, is higher in smoker patients than nonsmoker patients, and is induced by tobacco carcinogens in normal human lung epithelial cells. Forced expression of CDC34 promotes, whereas knockdown of CDC34 inhibits, NSCLC cell proliferation in vitro and in vivo. CDC34 competes with c-Cbl to bind Y1045 to inhibit polyubiquitination and degradation of EGFR. In EGFR-L858R and EGFR-T790M/Del (exon 19)-driven lung tumor growth in mouse models, knockdown of CDC34 significantly inhibits tumor formation.
interpretationThese results demonstrate that an E2 enzyme is capable of competing with E3 ligase to stabilize substrates, and CDC34 represents an attractive therapeutic target for NSCLCs.
fundingNational Key Research and Development Program of China, National Natural Science Foundation of China, and the CAMS Innovation Fund for Medical Sciences.
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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.