ArticlePloS one2013
NEDD4L is downregulated in colorectal cancer and inhibits canonical WNT signaling.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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The trial behind it
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Who cites it
49 citing papers in PubMed, 79 citations in OpenAlex.
- The SP1/NEDD4L Axis Suppresses the Breast Cancer Progression by Downregulating SNAI2 Expression.Biochemical genetics · 2026Article
- NEDD4L knockdown reduced lipid accumulation in non-alcoholic fatty liver disease by promoting the activity of PI3K/AKT signaling pathway.European journal of medical research · 2025Article
- PMEPA1 Binds NEDD4L to Inhibit the Malignant Progression of Multiple Myeloma by Inactivating Wnt/β-Catenin Signaling.Cell biochemistry and biophysics · 2025Article
- The E3 Ligase NEDD4L Prevents Colorectal Cancer Liver Metastasis via Degradation of PRMT5 to Inhibit the AKT/mTOR Signaling Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Reversal of endocrine resistance via N6AMT1-NEDD4L pathway-mediated p110α degradation.Oncogene · 2025Article
- Investigating the Causality and Pathogenesis of Primary Sclerosing Cholangitis in Colorectal Cancer Through Mendelian Randomization and Bioinformatics.Genetics research · 2025Article
- Morinda Officinalis Polysaccharides Inhibit Osteoclast Differentiation by Regulating miR-214-3p/NEDD4L in Postmenopausal Osteoporosis Mice.Calcified tissue international · 2024Article
- The E3 ubiquitin ligase Nedd4L preserves skeletal muscle stem cell quiescence by inhibiting their activation.iScience · 2024Article
- NEDD4 and NEDD4L: Ubiquitin Ligases Closely Related to Digestive Diseases.Biomolecules · 2024Review
- The E3 ubiquitin ligase NEDD4 regulates chemoresistance to 5-fluorouracil in colorectal cancer cells by altering JNK signalling.Cell death & disease · 2023Article
- Potential roles of NEDD4 and NEDD4L and their utility as therapeutic targets in high‑incidence adult male cancers (Review).Molecular and clinical oncology · 2023Review
- EGFR-T790M Mutation-Derived Interactome Rerouted EGFR Translocation Contributing to Gefitinib Resistance in Non-Small Cell Lung Cancer.Molecular & cellular proteomics : MCP · 2023Article
- The Role of HECT E3 Ubiquitin Ligases in Colorectal Cancer.Biomedicines · 2023Review
- NEDD4L in human tumors: regulatory mechanisms and dual effects on anti-tumor and pro-tumor.Frontiers in pharmacology · 2023Review
- NEDD4L inhibits glycolysis and proliferation of cancer cells in oral squamous cell carcinoma by inducing ENO1 ubiquitination and degradation.Cancer biology & therapy · 2022Article
- Unraveling the Potential Role of NEDD4-like E3 Ligases in Cancer.International journal of molecular sciences · 2022Review
- NEDD4L suppresses PD-L1 expression and enhances anti-tumor immune response in A549 cells.Genes & genomics · 2022Article
- NEDD4L inhibits cell viability, cell cycle progression, and glutamine metabolism in esophageal squamous cell carcinoma via ubiquitination of c-Myc.Acta biochimica et biophysica Sinica · 2022Article
- The Roles of NEDD4 Subfamily of HECT E3 Ubiquitin Ligases in Neurodevelopment and Neurodegeneration.International journal of molecular sciences · 2022Review
- Autophagy of the mNature communications · 2021Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The NEDD4 family of E3 ubiquitin ligases includes nine members. Each is a modular protein, containing an N-terminal C2 domain for cell localization, two-to-four central WW domains for substrate recognition, and a C-terminal, catalytic HECT domain, which is responsible for catalyzing the ubiquitylation reaction. Members of this family are known to affect pathways central to the pathogenesis of colorectal cancer, including the WNT, TGFβ, EGFR, and p53 pathways. Recently, NEDD4 mRNA was reported to be overexpressed in colorectal cancer, but tumor stage was not considered in the analysis. Expression of the other family members has not been studied in colorectal cancer. Herein, we determined the expression patterns of all nine NEDD4 family members in 256 patients who presented with disease ranging from premalignant adenoma to stage IV colorectal cancer. NEDD4 mRNA was significantly increased in all stages of colorectal cancer. In contrast, NEDD4L mRNA, the closest homolog to NEDD4, was the most highly downregulated family member, and was significantly downregulated in all tumor stages. We also found NEDD4L protein was significantly decreased by western blotting in colorectal cancer samples compared to adjacent normal mucosa. In addition, NEDD4L, but not catalytically inactive NEDD4L, inhibited canonical WNT signaling at or below the level of β-catenin in vitro. These findings suggest that NEDD4L may play a tumor suppressive role in colorectal cancer, possibly through inhibition of canonical WNT signaling.
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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.