ArticleSignal transduction and targeted therapy2021
HACE1-mediated NRF2 activation causes enhanced malignant phenotypes and decreased radiosensitivity of glioma cells.
Article in Signal transduction and targeted therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 27 citations in OpenAlex.
- Targeting E3 ubiquitin ligases: Mechanistic breakthroughs and novel clinical translation pathways for tumor radioimmunotherapy.Molecular cancer · 2026Review
- Cancer signaling networks in tumor progression and drug resistance: Crosstalk, adaptive reprogramming and therapeutic targeting (Review).Oncology reports · 2026Review
- TSC22D4 drives clear cell renal cell carcinoma progression and therapy resistance by stabilizing NRF2 through KEAP1 disruption.Cell death & disease · 2026Article
- HACE1 alleviates intervertebral disc degeneration by inhibiting ferroptosis in nucleus pulposus cells.Scientific reports · 2026Article
- Post-translational modification networks in tumor radiosensitivity: mechanistic insights and therapeutic opportunities.Journal of translational medicine · 2026Review
- miR-652-5p promoter hypermethylation enhances glioblastoma malignancy through the SDC1/TGFβ2/pERBB4 complex via HIF2α-mediated regulation under hypoxia.Cancer cell international · 2025Article
- MiR-646 inhibited cell proliferation and migration by targeting P62 in glioma.Cell adhesion & migration · 2025Article
- Article
- CircMAN1A2 Levels Determine GBM Susceptibility to TMZ in a Pathway Involving TEP1- and KEAP1-Mediated NRF2 Degradation Leading to Ferroptosis.CNS neuroscience & therapeutics · 2025Article
- HACE1 as a bridge between oxidative stress and autophagy.Frontiers in immunology · 2025Review
- LINC00161 upregulated by M2-like tumor-associated macrophages promotes hepatocellular carcinoma progression by methylating HACE1 promoters.Cytotechnology · 2024Article
- Article
- Unveiling the role of HACE1 in cervical cancer: implications for human papillomavirus infection and prognosis.Translational cancer research · 2024Article
- Article
- CYLD induces high oxidative stress and DNA damage through class I HDACs to promote radiosensitivity in nasopharyngeal carcinoma.Cell death & disease · 2024Article
- Polyphenols alleviate metabolic disorders: the role of ubiquitin-proteasome system.Frontiers in nutrition · 2024Review
- The Mechanism of Ubiquitination or Deubiquitination Modifications in Regulating Solid Tumor Radiosensitivity.Biomedicines · 2023Review
- Article
- Uncovering the Secrets of Prostate Cancer's Radiotherapy Resistance: Advances in Mechanism Research.Biomedicines · 2023Review
- Ubiquitin-modifying enzymes in Huntington's disease.Frontiers in molecular biosciences · 2023Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HACE1, an E3 ubiquitin-protein ligase, is frequently inactivated and has been evidenced as a putative tumor suppressor in different types of cancer. However, its role in glioma remains elusive. Here, we observed increased expression of HACE1 in gliomas related to control subjects, and found a strong correlation of high HACE1 expression with poor prognosis in patients with WHO grade III and IV as well as low-grade glioma (LGG) patients receiving radiotherapy. HACE1 knockdown obviously suppressed malignant behaviors of glioma cells, while ectopic expression of HACE1 enhanced cell growth in vitro and in vivo. Further studies revealed that HACE1 enhanced protein stability of nuclear factor erythroid 2-related factor 2 (NRF2) by competitively binding to NRF2 with another E3 ligase KEAP1. Besides, HACE1 also promoted internal ribosome entry site (IRES)-mediated mRNA translation of NRF2. These effects did not depend on its E3 ligase activity. Finally, we demonstrated that HACE1 dramatically reduced cellular ROS levels by activating NRF2, thereby decreasing the response of glioma cells to radiation. Altogether, our data demonstrate that HACE1 causes enhanced malignant phenotypes and decreased radiosensitivity of glioma cells by activating NRF2, and indicate that it may act as the role of prognostic factor and potential therapeutic target in glioma.
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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.