ArticleThe Journal of clinical investigation2018
TRAF4-mediated ubiquitination of NGF receptor TrkA regulates prostate cancer metastasis.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 80 citations in OpenAlex.
- TRAF4 promotes nasopharyngeal carcinoma progression by stabilizing SETDB1 to suppress mitochondrial apoptosis.Molecular and cellular biochemistry · 2026Article
- TRIM15 Mediates ubiquitination of Paxillin to facilitate the progression of ovarian cancer.Cancer cell international · 2026Article
- Tumour necrosis factor receptor-associated factor 7 drives leukaemogenesis through the TWIST1-P2RX1-CaJournal of translational medicine · 2026Article
- Mast-cell derived nerve growth factor drives ILC2 pro-tumoral functions in bladder cancer.Nature communications · 2026Article
- Research Advances in Drug Resistance Mechanisms to Anti-HER2 Therapy in HER2-Positive Breast Cancer.Oncology research · 2026Review
- Peripheral nerve remodeling in the tumor microenvironment: neuro-immune crosstalk, molecular mechanisms, and precision therapeutic.Frontiers in immunology · 2026Review
- The Crosstalk Between CRL5 and APC/C E3 Ligases Regulates Metastasis and Chemosensitivity of Cancer Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- OrthogonalApplied and environmental microbiology · 2025Article
- Fibroblasts promote the progression of benign prostatic hyperplasia through colony-stimulating factor 1 receptor-mediated RTK signaling in prostatic epithelial cells.Molecular biomedicine · 2025Article
- Tumor Innervation: From Bystander to Emerging Therapeutic Target for Cancer.International journal of molecular sciences · 2025Review
- Nerve growth factor: what can surgeons and oncologists learn from a neurological and psychological biomarker?Molecular medicine (Cambridge, Mass.) · 2025Review
- Targeting nerve growth factor: an Achilles' heel for tumors?Journal for immunotherapy of cancer · 2025Article
- Identification of E3 Ubiquitin Ligase Substrates Using Biotin Ligase-Based Proximity Labeling Approaches.Biomedicines · 2025Review
- Nerve Growth Factor Signaling Promotes Nuclear Translocation of TRAF4 to Enhance Tumor Stemness and Metastatic Dormancy Via C-Jun-mediated IL-8 Autocrine.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The role of ubiquitination and deubiquitination in urological tumours.Frontiers in pharmacology · 2025Review
- Mechanisms of neural infiltration-mediated tumor metabolic reprogramming impacting immunotherapy efficacy in non-small cell lung cancer.Journal of experimental & clinical cancer research : CR · 2024Article
- Ubiquitination Process Mediates Prostate Cancer Development and Metastasis through Multiple Mechanisms.Cell biochemistry and biophysics · 2024Review
- Ubiquitin B, Ubiquitin C, and β-Catenin as Promising Diagnostic and Prognostic Tools in Prostate Cancer.Cancers · 2024Article
- Cand2 inhibits CRL-mediated ubiquitination and suppresses autophagy to facilitate pathogenicity of phytopathogenic fungi.Plant communications · 2024Article
- Heart Failure Post-Myocardial Infarction Promotes Mammary Tumor Growth Through the NGF-TRKA Pathway.JACC. CardioOncology · 2024Article
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10 authors at 3 institutions in 1 country.
Funding
Abstract
Receptor tyrosine kinases (RTKs) are important drivers of cancers. In addition to genomic alterations, aberrant activation of WT RTKs plays an important role in driving cancer progression. However, the mechanisms underlying how RTKs drive prostate cancer remain incompletely characterized. Here we show that non-proteolytic ubiquitination of RTK regulates its kinase activity and contributes to RTK-mediated prostate cancer metastasis. TRAF4, an E3 ubiquitin ligase, is highly expressed in metastatic prostate cancer. We demonstrated here that it is a key player in regulating RTK-mediated prostate cancer metastasis. We further identified TrkA, a neurotrophin RTK, as a TRAF4-targeted ubiquitination substrate that promotes cancer cell invasion and found that inhibition of TrkA activity abolished TRAF4-dependent cell invasion. TRAF4 promoted K27- and K29-linked ubiquitination at the TrkA kinase domain and increased its kinase activity. Mutation of TRAF4-targeted ubiquitination sites abolished TrkA tyrosine autophosphorylation and its interaction with downstream proteins. TRAF4 knockdown also suppressed nerve growth factor (NGF) stimulated TrkA downstream p38 MAPK activation and invasion-associated gene expression. Furthermore, elevated TRAF4 levels significantly correlated with increased NGF-stimulated invasion-associated gene expression in prostate cancer patients, indicating that this signaling axis is significantly activated during oncogenesis. Our results revealed a posttranslational modification mechanism contributing to aberrant non-mutated RTK activation in cancer cells.
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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.