ArticleJournal of cellular and molecular medicine2019
p62 aggregates mediated Caspase 8 activation is responsible for progression of ovarian cancer.
Article in Journal of cellular and molecular medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 52 citations in OpenAlex.
- UBE2N deficiency contributes to MASH development via p62-regulated mitophagy and PANoptosis.Nature metabolism · 2026Article
- Non-canonical signaling hubs upon inhibition of MyD88-ERK interaction in cancer.Cell death & disease · 2026Article
- α-Synuclein Deletion Leads to Hyposmia: due to Defective Autophagy Induced by Abnormal PI3K/mTOR Signaling Pathway in Olfactory Bulb.Molecular neurobiology · 2026Article
- p62/SQSTM1 signaling nexus and orchestration of ERK and mTOR pathways are crucial for Bacoside A- induced autophagy-mediated apoptosis in chronic myelogenous leukemia.Archives of pharmacal research · 2025Article
- Autophagy and exosome dynamics in Radiation-Induced pulmonary fibrosis: the critical role of TRIB3.Respiratory research · 2025Article
- Scutellaria barbata D.Don and Hedyotis diffusa Willd herb pair combined with cisplatin synergistically inhibits ovarian cancer progression through modulating oxidative stress via NRF2-FTH1 autophagic degradation pathway.Journal of ovarian research · 2024Article
- Ally or traitor: the dual role of p62 in caspase-2 regulation.Cell death & disease · 2024Article
- Zinc finger domain of p62/SQSTM1 is involved in the necroptosis of human cisplatin‑resistant ovarian cancer cells treated with sulfasalazine.Oncology letters · 2024Article
- 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
- Different Roles of Apoptosis and Autophagy in the Development of Human Colorectal Cancer.International journal of molecular sciences · 2023Review
- Role of autophagy and its regulation by noncoding RNAs in ovarian cancer.Experimental biology and medicine (Maywood, N.J.) · 2023Review
- Inhibition of autophagy; an opportunity for the treatment of cancer resistance.Frontiers in cell and developmental biology · 2023Review
- The non-apoptotic function of Caspase-8 in negatively regulating the CDK9-mediated Ser2 phosphorylation of RNA polymerase II in cervical cancer.Cellular and molecular life sciences : CMLS · 2022Article
- Itaconic Acid as A Differential Transcription Regulator of Apoptosis and Autophagy Pathways Genes: A Rat Adipose Mesenchymal Stem Cells Model.Cell journal · 2022Article
- Quercetin induces autophagy-associated death in HL-60 cells through CaMKKβ/AMPK/mTOR signal pathway.Acta biochimica et biophysica Sinica · 2022Article
- BAG family proteins contributes to autophagy-mediated multidrug resistance of tumor.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Review
- p62 Promotes the Mitochondrial Localization of p53 through Its UBA Domain and Participates in Regulating the Sensitivity of Ovarian Cancer Cells to Cisplatin.International journal of molecular sciences · 2022Article
- The Pathomechanism, Antioxidant Biomarkers, and Treatment of Oxidative Stress-Related Eye Diseases.International journal of molecular sciences · 2022Review
- Sequestosome 1/p62: A multitasker in the regulation of malignant tumor aggression (Review).International journal of oncology · 2021Review
- S-Adenosylmethionine Increases the Sensitivity of Human Colorectal Cancer Cells to 5-Fluorouracil by Inhibiting P-Glycoprotein Expression and NF-κB Activation.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Increasing evidence suggests that p62/SQSTM1 functions as a signalling centre in cancer. However, the role of p62 in tumour development depends on the interacting factors it recruits and its precise regulatory mechanism remains unclear. In this study, we investigated the pro-death signalling recruitment of p62 with the goal of improving anti-tumour drug effects in ovarian cancer treatment. We found that p62 with Caspase 8 high expression is correlated with longer survival time compared with cases of low Caspase 8 expression in ovarian cancer. In vivo experiments suggested that insoluble p62 and ubiquitinated protein accumulation induced by autophagy impairment promoted the activation of Caspase 8 and increased cell sensitivity to cisplatin. Furthermore, p62 functional domain UBA and LIR mutants regulated autophagic flux and attenuated Caspase 8 activation, which indicates that autophagic degradation is involved in p62-mediated activation of Caspase 8 in ovarian cancer cells. Collectively, our study demonstrates that p62 promotes Caspase 8 activation through autophagy flux blockage with cisplatin treatment. We have provided evidence that autophagy induction followed by its blockade increases cell sensitivity to chemotherapy which is dependent on p62-Caspase 8 mediated apoptosis signalling. p62 exhibits pro-death functions through its interaction with Caspase 8. p62 and Caspase 8 may become novel prognostic biomarkers and oncotargets for ovarian cancer treatment.
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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.