ArticleCell death & disease2021
Epigenetic regulation of p62/SQSTM1 overcomes the radioresistance of head and neck cancer cells via autophagy-dependent senescence induction.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 42 citations in OpenAlex.
- Platycodin D sensitizes head and neck squamous cell carcinoma to cisplatin by inducing autophagy arrest.Oncology reports · 2026Article
- Targeting ferroptosis mediated cell death: a novel strategy for mitigating acute pancreatitis.Molecular biology reports · 2026Review
- Abscopal effect induced by conventional fractionated radiotherapy following anti-PD-1 immunotherapy in pulmonary metastatic thymic squamous cell carcinoma: a case report and literature review.Frontiers in immunology · 2026Review
- Drug-tolerant persister cells in head and neck squamous cell carcinoma: Molecular mechanisms and therapeutic opportunities.Translational oncology · 2026Article
- Cellular senescence in cancer: from mechanism paradoxes to precision therapeutics.Molecular cancer · 2025Review
- The CRISPR-Cas revolution in head and neck cancer: a new era of targeted therapy.Functional & integrative genomics · 2025Review
- NAP1L1 degradation by FBXW7 reduces the deubiquitination of HDGF-p62 signaling to stimulate autophagy and induce primary cisplatin chemosensitivity in nasopharyngeal carcinoma.Molecular cancer · 2025Article
- CRISPR/Cas9 system: a novel approach to overcome chemotherapy and radiotherapy resistance in cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- The methylation-expression correlation of autophagy-related genes in colorectal cancer patients from southern Iran.Molecular biology research communications · 2025Article
- Cellular senescence and metabolic reprogramming: Unraveling the intricate crosstalk in the immunosuppressive tumor microenvironment.Cancer communications (London, England) · 2024Review
- Nanoparticle-delivered quercetin exhibits enhanced efficacy in eliminating iron-overloaded senescent chondrocytes.Nanomedicine (London, England) · 2024Article
- Epigenetics in the formation of pathological aggregates in amyotrophic lateral sclerosis.Frontiers in molecular neuroscience · 2024Review
- The sequestosome 1 protein: therapeutic vulnerabilities in ovarian cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Review
- A Comprehensive Review of Natural Products as Therapeutic or Chemopreventive Agents against Head and Neck Squamous Cell Carcinoma Cells Using Preclinical Models.Biomedicines · 2023Review
- ATHENA: an independently validated autophagy-related epigenetic prognostic prediction model of head and neck squamous cell carcinoma.Clinical epigenetics · 2023Article
- Article
- NEDD8 promotes radioresistance via triggering autophagy formation and serves as a novel prognostic marker in oral squamous cell carcinoma.Cancer cell international · 2023Article
- Autophagy impairment in patients with obstructive sleep apnea modulates intermittent hypoxia-induced oxidative stress and cell apoptosis via hypermethylation of the ATG5 gene promoter region.European journal of medical research · 2023Article
- Epigenetic regulation of RARB overcomes the radio-resistance of colorectal carcinoma cells via cancer stem cells.Journal of radiation research · 2023Article
- The Advances in Epigenetics for Cancer Radiotherapy.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumors are composed of subpopulations of cancer cells with functionally distinct features. Intratumoral heterogeneity limits the therapeutic effectiveness of cancer drugs. To address this issue, it is important to understand the regulatory mechanisms driving a subclonal variety within a therapy-resistant tumor. We identified tumor subclones of HN9 head and neck cancer cells showing distinct responses to radiation with different levels of p62 expression. Genetically identical grounds but epigenetic heterogeneity of the p62 promoter regions revealed that radioresistant HN9-R clones displayed low p62 expression via the creation of repressive chromatin architecture, in which cooperation between DNMT1 (DNA methyltransferases 1) and HDAC1 (histone deacetylases 1) resulted in DNA methylation and repressive H3K9me3 and H3K27me3 marks in the p62 promoter. Combined inhibition of DNMT1 and HDAC1 by genetic depletion or inhibitors enhanced the suppressive effects on proliferative capacity and in vivo tumorigenesis following irradiation. Importantly, ectopically p62-overexpressed HN9-R clones increased the induction of senescence along with p62-dependent autophagy activation. These results demonstrate the heterogeneous expression of p62 as the key component of clonal variation within a tumor against irradiation. Understanding the epigenetic diversity of p62 heterogeneity among subclones allows for improved identification of the functional state of subclones and provides a novel treatment option to resolve resistance to current therapies.
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