ArticleCell death & disease2021
p62/SQSTM1-induced caspase-8 aggresomes are essential for ionizing radiation-mediated apoptosis.
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 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- The dual role of autophagy in HPV-positive head and neck squamous cell carcinoma: a systematic review.Journal of cancer research and clinical oncology · 2024Pooled it
- Hypoxia, metastatic origin and HPV16 E6/E7 expression differentially shape the radiation response in head and neck squamous cell carcinoma cell lines.Scientific reports · 2026Article
- Unraveling key molecules mediating the mechanisms of YAP deletion or inhibition in liver fibrosis regression through a multi-omics approach.Histology and histopathology · 2026Article
- α-Synuclein Deletion Leads to Hyposmia: due to Defective Autophagy Induced by Abnormal PI3K/mTOR Signaling Pathway in Olfactory Bulb.Molecular neurobiology · 2026Article
- The multifaceted role of SQSTM1/p62 in disc degeneration: A master regulator of cellular stress responses.Biochemistry and biophysics reports · 2025Review
- EMT-ciliary signaling in quasi-mesenchymal-stem-like cells drives therapeutic resistance and is a druggable vulnerability in triple-negative breast cancer.EMBO molecular medicine · 2025Article
- NAE1-mediated neddylation coordinates ubiquitination regulation of meiotic recombination during spermatogenesis.Theranostics · 2025Article
- UnravelingFrontiers in pharmacology · 2025Review
- Ally or traitor: the dual role of p62 in caspase-2 regulation.Cell death & disease · 2024Article
- c-Jun N-terminal Kinase Supports Autophagy in Testicular Ischemia but Triggers Apoptosis in Ischemia-Reperfusion Injury.International journal of molecular sciences · 2024Article
- Protein Aggregates and Aggrephagy in Myopathies.International journal of molecular sciences · 2023Review
- NF-κB/RelA controlled A20 limits TRAIL-induced apoptosis in pancreatic cancer.Cell death & disease · 2023Article
- A radiobiological perspective on radioresistance or/and radiosensitivity of head and neck squamous cell carcinoma.Reports of practical oncology and radiotherapy : journal of Greatpoland Cancer Center in Poznan and Polish Society of Radiation Oncology · 2023Review
- Article
- Investigation and experimental validation of curcumin-related mechanisms against hepatocellular carcinoma based on network pharmacology.Journal of Zhejiang University. Science. B · 2022Article
- Dehydroepiandrosterone exacerbates nigericin-induced abnormal autophagy and pyroptosis via GPER activation in LPS-primed macrophages.Cell death & disease · 2022Article
- Alterations in Proteostasis System Components in Peripheral Blood Mononuclear Cells in Parkinson Disease: Focusing on the HSP70 and p62 Levels.Biomolecules · 2022Article
- SQSTM1/p62 as a therapeutic target in cancer.Autophagy reports · 2022Article
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Authors and funding
15 authors at 3 institutions in 3 countries.
Funding
Abstract
The autophagy-lysosome pathway and apoptosis constitute vital determinants of cell fate and engage in a complex interplay in both physiological and pathological conditions. Central to this interplay is the archetypal autophagic cargo adaptor p62/SQSTM1/Sequestosome-1 which mediates both cell survival and endoplasmic reticulum stress-induced apoptosis via aggregation of ubiquitinated caspase-8. Here, we investigated the role of p62-mediated apoptosis in head and neck squamous cell carcinoma (HNSCC), which can be divided into two groups based on human papillomavirus (HPV) infection status. We show that increased autophagic flux and defective apoptosis are associated with radioresistance in HPV(-) HNSCC, whereas HPV(+) HNSCC fail to induce autophagic flux and readily undergo apoptotic cell death upon radiation treatments. The degree of radioresistance and tumor progression of HPV(-) HNSCC respectively correlated with autophagic activity and cytosolic levels of p62. Pharmacological activation of the p62-ZZ domain using small molecule ligands sensitized radioresistant HPV(-) HNSCC cells to ionizing radiation by facilitating p62 self-polymerization and sequestration of cargoes leading to apoptosis. The self-polymerizing activity of p62 was identified as the essential mechanism by which ubiquitinated caspase-8 is sequestered into aggresome-like structures, without which irradiation fails to induce apoptosis in HNSCC. Our results suggest that harnessing p62-dependent sequestration of ubiquitinated caspase-8 provides a novel therapeutic avenue in patients with radioresistant tumors.
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Registered trials
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.