ArticleNature communications2015
TRB3 links insulin/IGF to tumour promotion by interacting with p62 and impeding autophagic/proteasomal degradations.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 2 of them syntheses that pooled it.
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91 citing papers in PubMed, 2 syntheses or guidelines pooled it, 139 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).Autophagy · 2016Guideline
- Crosstalk Between Autophagy and Paraptosis: A New Frontier in Cancer Therapy.International journal of molecular sciences · 2026Review
- TEAD4 Transcriptionally Activates TRIB3 to Induce Ferroptosis Resistance through the MEK/ERK Signaling Pathway in Colorectal Cancer.Gut and liver · 2025Article
- Autophagy and exosome dynamics in Radiation-Induced pulmonary fibrosis: the critical role of TRIB3.Respiratory research · 2025Article
- RNA NCell death & disease · 2025Article
- The emerging role of E3 ubiquitin ligases and deubiquitinases in metabolic dysfunction-associated steatotic liver disease.Journal of translational medicine · 2025Review
- CUL1-neddylation contributes to K29-linked ubiquitination on p27 for autophagic degradation in sorafenib-resistant liver cancer.Cell biology and toxicology · 2025Article
- Pseudokinase TRIB3 stabilizes SSRP1 via USP10-mediated deubiquitination to promote multiple myeloma progression.Oncogene · 2025Article
- Blue Light Damages Retinal Ganglion Cells Via Endoplasmic Reticulum Stress and Autophagy in Chickens.Investigative ophthalmology & visual science · 2025Article
- Cell-permeated peptide P-T3H2 inhibits malignancy on hepatocellular carcinoma through stabilizing HNF4α protein.Discover oncology · 2024Article
- Tribbles pseudokinase 3 promotes enterovirus A71 infection via dual mechanisms.Emerging microbes & infections · 2024Article
- T1/T2 Proportional Magnetic Resonance Nanoprobe Monitoring Tumor Autophagy during Chemotherapy.Nanomaterials (Basel, Switzerland) · 2024Article
- Enhancing terminal erythroid differentiation in human embryonic stem cells through TRIB3 overexpression.Heliyon · 2024Article
- Supramolecular Nanofibers Ameliorate Bleomycin-Induced Pulmonary Fibrosis by Restoring Autophagy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- TRIB3 promotes the progression of renal cell carcinoma by upregulating the lipid droplet-associated protein PLIN2.Cell death & disease · 2024Article
- Interplay of p62-mTORC1 and EGFR signaling promotes cisplatin resistance in oral cancer.Heliyon · 2024Article
- Oral Carbon Monoxide Enhances Autophagy Modulation in Prostate, Pancreatic, and Lung Cancers.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Integration of dietary nutrition and TRIB3 action into diabetes mellitus.Nutrition reviews · 2024Review
- Developing an advanced diagnostic model for hepatocellular carcinoma through multi-omics integration leveraging diverse cell-death patterns.Frontiers in immunology · 2024Article
31 more citing papers are in PubMed but not listed here.
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15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High insulin/IGF is a biologic link between diabetes and cancers, but the underlying molecular mechanism remains unclear. Here we report a previously unrecognized tumour-promoting mechanism for stress protein TRB3, which mediates a reciprocal antagonism between autophagic and proteasomal degradation systems and connects insulin/IGF to malignant promotion. We find that several human cancers express higher TRB3 and phosphorylated insulin receptor substrate 1, which correlates negatively with patient's prognosis. TRB3 depletion protects against tumour-promoting actions of insulin/IGF and attenuates tumour initiation, growth and metastasis in mice. TRB3 interacts with autophagic receptor p62 and hinders p62 binding to LC3 and ubiquitinated substrates, which causes p62 deposition and suppresses autophagic/proteasomal degradation. Several tumour-promoting factors accumulate in cancer cells to support tumour metabolism, proliferation, invasion and metastasis. Interrupting TRB3/p62 interaction produces potent antitumour efficacies against tumour growth and metastasis. Our study opens possibility of targeting this interaction as a potential novel strategy against cancers with diabetes.
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