ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2020
EGF Relays Signals to COP1 and Facilitates FOXO4 Degradation to Promote Tumorigenesis.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 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 25 papers.
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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
25 citing papers in PubMed, 33 citations in OpenAlex.
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- CSN6 Promotes Pancreatic Cancer Progression and Gemcitabine Resistance via Antagonizing DCAF1-Mediated Ubiquitination of NPM1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Application of Gene Editing Technology Based on Targeted Delivery Materials in TNBC.ACS omega · 2025Review
- ACAA2 Protects Against Cardiac Dysfunction and Lipid Peroxidation in Renal Insufficiency with the Treatment of S-Nitroso-L-Cysteine.Biomolecules · 2025Article
- EGF-Upregulated lncRNA ESSENCE Promotes Colorectal Cancer Growth through Stabilizing CAD and Ferroptosis Defense.Research (Washington, D.C.) · 2025Article
- Pseudokinase STK40 promotes TScience advances · 2024Article
- CSN6-SPOP-HMGCS1 Axis Promotes Hepatocellular Carcinoma Progression via YAP1 Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- The involvement of E3 ubiquitin ligases in the development and progression of colorectal cancer.Cell death discovery · 2023Review
- eIF3f Mediates SGOC Pathway Reprogramming by Enhancing Deubiquitinating Activity in Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- COPS6 promotes tumor progression and reduces CD8Acta pharmacologica Sinica · 2023Article
- ACTL6A protects gastric cancer cells against ferroptosis through induction of glutathione synthesis.Nature communications · 2023Article
- FBXW7β loss-of-function enhances FASN-mediated lipogenesis and promotes colorectal cancer growth.Signal transduction and targeted therapy · 2023Article
- Role of the gut microbiota in anticancer therapy: from molecular mechanisms to clinical applications.Signal transduction and targeted therapy · 2023Review
- Tespa1 facilitates hematopoietic and leukemic stem cell maintenance by restricting c-Myc degradation.Leukemia · 2023Article
- The chromatin remodeler CHD6 promotes colorectal cancer development by regulating TMEM65-mediated mitochondrial dynamics via EGF and Wnt signaling.Cell discovery · 2022Article
- Roles of lncRNA LVBU in regulating urea cycle/polyamine synthesis axis to promote colorectal carcinoma progression.Oncogene · 2022Article
- UBP12 and UBP13 deubiquitinases destabilize the CRY2 blue light receptor to regulate Arabidopsis growth.Current biology : CB · 2022Article
- Metabolomic analyses reveal new stage-specific features of COVID-19.The European respiratory journal · 2022Article
- Harness the functions of gut microbiome in tumorigenesis for cancer treatment.Cancer communications (London, England) · 2021Review
- Impact of diabetes on promoting the growth of breast cancer.Cancer communications (London, England) · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Forkhead-Box Class O 4 (FOXO4) is involved in critical biological functions, but its response to EGF-PKB/Akt signal regulation is not well characterized. Here, it is reported that FOXO4 levels are downregulated in response to EGF treatment, with concurrent elevation of COP9 Signalosome subunit 6 (CSN6) and E3 ubiquitin ligase constitutive photomorphogenic 1 (COP1) levels. Mechanistic studies show that CSN6 binds and regulates FOXO4 stability through enhancing the E3 ligase activity of COP1, and that COP1 directly interacts with FOXO4 through a VP motif on FOXO4 and accelerates the ubiquitin-mediated degradation of FOXO4. Metabolomic studies demonstrate that CSN6 expression leads to serine and glycine production. It is shown that FOXO4 directly binds and suppresses the promoters of serine-glycine-one-carbon (SGOC) pathway genes, thereby diminishing SGOC metabolism. Evidence shows that CSN6 can regulate FOXO4-mediated SGOC gene expression. Thus, these data suggest a link of CSN6-FOXO4 axis and ser/gly metabolism. Further, it is shown that CSN6-COP1-FOXO4 axis is deregulated in cancer and that the protein expression levels of CSN6 and FOXO4 can serve as prognostic markers for cancers. The results illustrate a pathway regulation of FOXO4-mediated serine/glycine metabolism through the function of CSN6-COP1 axis. Insights into this pathway may be strategically designed for therapeutic intervention in cancers.
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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.