ArticleAutophagy2019
TRAF6 inhibits colorectal cancer metastasis through regulating selective autophagic CTNNB1/β-catenin degradation and is targeted for GSK3B/GSK3β-mediated phosphorylation and degradation.
Article in Autophagy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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Who cites it
87 citing papers in PubMed, 134 citations in OpenAlex.
- Intestinal epithelial GSK3β governs fumarate-dependent neutrophil reprogramming to promote colorectal cancer.Nature cancer · 2026Article
- WDR23 prevents bone loss by promoting autophagic degradation of TRAF6 in osteoclastogenesis.Bone research · 2026Article
- ARID1A regulates colorectal cancer metastasis through the AKT/mTOR/p70S6K pathway.Translational oncology · 2026Article
- Study on the Antidepressant Effect and Mechanism of Water Extract of Semiliquidambar cathayensis (WESC) Based on the GSK3β/NF-κB Signaling Pathway.Chemistry & biodiversity · 2026Article
- 10-Hydroxy-2-decenoic Acid Suppresses Colorectal Cancer Progression by Inhibiting Wnt/β-Catenin Signaling and Promoting Apoptosis.Foods (Basel, Switzerland) · 2026Article
- Review
- Annexin A3 potentiates lenvatinib resistance in hepatocellular carcinoma through multiple approaches amplified by a positive feedback loop.Cell death & disease · 2026Article
- Extracellular CD44 lactylation impairs CD8Nature metabolism · 2026Article
- CB2R-mediated GPX4 stabilization: a new avenue for treating cognitive impairment in elderly migraine patients.The journal of headache and pain · 2026Article
- Prognostic and Immunological Value of CTNNB1 in Pancreatic Adenocarcinoma: A Comprehensive NGS and Multicomponent Analysis.Genetics research · 2026Article
- Ubiquitination mediated by RING-type E3 ligases in the progression of digestive system tumors: mechanistic insights and potential therapeutic strategies.Frontiers in cell and developmental biology · 2026Review
- Immunoregulatory roles of post-translational modifications in colorectal cancer: mechanisms and therapeutic implications.Cellular and molecular life sciences : CMLS · 2025Review
- Identification of a novel ferroptosis-related gene signature in hepatocellular carcinoma: clinical significance, tumor microenvironment, drug sensitivity, and gene landscape analysis.Discover oncology · 2025Article
- Evaluation of the Circadian Rhythm Component Cipc (Clock-Interacting Pacemaker) in Leukemogenesis: A Literature Review and Bioinformatics Approach.Clocks & sleep · 2025Review
- E3 ubiquitin ligase RNF128 attenuates colitis and colorectal tumorigenesis by triggering the degradation of IL-6 receptors.Journal of advanced research · 2025Article
- Fatty acid synthase inhibition alleviates lung fibrosis via β-catenin signal in fibroblasts.Life science alliance · 2025Article
- Role of Ubiquitin-regulated EMT in Cancer Metastasis and Chemoresistance.International journal of biological sciences · 2025Review
- Embryonic Lethal Abnormal Visual-Like Protein 1 Aggravates Caerulein-Induced AR42J Cell Injury and Macrophage M1 Polarization to Accelerate Acute Pancreatitis by Upregulating TRAF6.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2025Article
- DLX2 promotes gastric cancer epithelial- mesenchymal transition and malignant progression through the PI3K/AKT signaling pathway.Frontiers in oncology · 2025Article
- Molecular Mechanism of TRAF6 in Malignant Proliferation of Human NK/T Cell Lymphoma Cell HANK1.Mediterranean journal of hematology and infectious diseases · 2025Article
27 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant CTNNB1 signaling is one of the fundamental processes in cancers, especially colorectal cancer (CRC). Here, we reported that TRAF6, an E3 ubiquitin ligase important for inflammatory signaling, inhibited epithelial-mesenchymal transition (EMT) and CRC metastasis through driving a selective autophagic CTNNB1 degradation machinery. Mechanistically, TRAF6 interacted with MAP1LC3B/LC3B through its LC3-interacting region 'YxxL' and catalyzed K63-linked polyubiquitination of LC3B. The K63-linked ubiquitination of LC3B promoted the formation of the LC3B-ATG7 complex and was critical to the subsequent recognition of CTNNB1 by LC3B for the selective autophagic degradation. However, TRAF6 was phosphorylated at Thr266 by GSK3B in most clinical CRC, which triggered K48-linked polyubiquitination and degradation of TRAF6 and thereby attenuated its inhibitory activity towards the autophagy-dependent CTNNB1 signaling. Clinically, decreased expression of TRAF6 was associated with elevated GSK3B protein levels and activity and reduced overall survival in CRC patients. Pharmacological inhibition of GSK3B activity stabilized the TRAF6 protein, promoted CTNNB1 degradation, and effectively suppressed EMT and CRC metastasis. Thus, targeting TRAF6 and its pathway may be meaningful for treating advanced CRC.
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