ArticleCell death and differentiation2023
The TRAF2-p62 axis promotes proliferation and survival of liver cancer by activating mTORC1 pathway.
Article in Cell death and differentiation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 34 citations in OpenAlex.
- Structural dynamics and pH-regulated membrane binding of the TRAF2-NC trimer.Protein science : a publication of the Protein Society · 2026Article
- [Everolimus inhibits malignant phenotype of erdafitinib-resistant bladder cancer cells through the p70S6K/PI3K/MAPK signaling pathway].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- OTUB1 inhibits autophagy-dependent ferroptosis in hepatocellular carcinoma by stabilizing p62 via non-canonical deubiquitination.Cell death discovery · 2026Article
- Identification and functional validation of SPON2 as a novel biomarker for the diagnosis and prognosis in hepatocellular carcinoma.Journal of gastrointestinal oncology · 2026Article
- Emerging role of proteomics in advancing diagnosis, prognosis, and treatment of liver cancer.Liver research (Beijing, China) · 2026Review
- The oncogenic signalosome: SQSTM1/p62 as a master integrator of signaling, metabolism, and autophagy in cancer.Toxicological research · 2026Review
- Low-dose TNF-α drives malignant progression and lipid metabolism in glioblastoma through the TRAF2-FASN axis.Cell death discovery · 2026Article
- Article
- Ubiquitin-centered post-translational modification crosstalk orchestrates tumor immunity and immunotherapy response.Experimental hematology & oncology · 2026Review
- TRIM38 Suppresses Breast Cancer Progression via Modulating SQSTM1 Ubiquitination and Autophagic Flux.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- TRIM39 aggravates hepatocellular carcinoma growth through targeting the p62-KEAP1-NRF2 axis.Scientific reports · 2025Article
- UCHL3: a crucial deubiquitinase in DNA damage repair and tumor progression.Cancer cell international · 2025Review
- Review
- Inflammation and cancer cell survival: TRAF2 as a key player.Cell death & disease · 2025Review
- ASB1 engages with ELOB to facilitate SQOR ubiquitination and HRedox biology · 2025Article
- Ubiquitination of CD47 Regulates Innate Anti-Tumor Immune Response.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The role of TRAF2 in pan-cancer revealed by integrating informatics and experimental validation.Frontiers in pharmacology · 2025Article
- TRAF2 Promotes Liver Fibrosis via Regulation of the HIF-1α/GLUT1-Mediated Glycolysis in Hepatic Stellate Cells.International journal of biological sciences · 2025Article
- Lactoferrin targeting INTL1 receptor inhibits hepatocellular carcinoma progression via apoptosis and cell cycle signaling pathways.Scientific reports · 2024Article
- Targeting autophagy in HCC treatment: exploiting the CD147 internalization pathway.Cell communication and signaling : CCS · 2024Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TRAF2 (Tumor necrosis factor receptor-associated factor 2) is a dual function protein, acting as an adaptor protein and a ubiquitin E3 ligase, which plays an essential role in mediating the TNFα-NFκB signal pathway. Dysregulated expression of TRAF2 has been reported in a variety of human cancers. Whether and how TRAF2 regulates the growth of liver cancer cells remains elusive. The goal of this study is to investigate potential dysregulation of TRAF2 and its biological function in liver cancer, and to elucidate the underlying mechanism, leading to validation of TRAF2 as an attractive liver cancer target. Here, we reported TRAF2 is up-regulated in human liver cancer cell lines and tissues, and high TRAF2 expression is associated with a poor prognosis of HCC patients. Proteomics profiling along with Co-immunoprecipitation analysis revealed that p62 is a new substrate of TRAF2, which is subjected to TRAF2-induced polyubiquitination via the K63 linkage at the K420 residue. A strong negative correlation was found between the protein levels of p62 and TRAF2 in human HCC samples. TRAF2 depletion inhibited growth and survival of liver cancer cells both in vitro and in vivo by causing p62 accumulation, which is partially rescued by simultaneous p62 knockdown. Mechanistically, TRAF2-mediated p62 polyubiquitylation activates the mTORC1 by forming the p62-mTORC1-Rag complex, which facilitates the lysosome localization of mTORC1. TRAF2 depletion inhibited mTORC1 activity through the disruption of interaction between p62 and the mTORC1 complex. In conclusion, our study provides the proof-of-concept evidence that TRAF2 is a valid target for liver cancer.
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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 Socratic graph.