ArticlePloS one2014
p62/SQSTM1 accumulation in squamous cell carcinoma of head and neck predicts sensitivity to phosphatidylinositol 3-kinase pathway inhibitors.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- Isotype-specific antibody secreting plasma cells harbor epigenetic and transcription factor architectures defining distinct cell lineages.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- The Roles of SQSTM1/p62 in Selective Autophagy and Oncogenic Signaling.International journal of molecular sciences · 2026Review
- p62/SQSTM1 in cancer: phenomena, mechanisms, and regulation in DNA damage repair.Cancer metastasis reviews · 2025Review
- Autophagy and nuclear morphometry are associated with histopathologic features in esophageal squamous cell carcinoma.Journal of molecular medicine (Berlin, Germany) · 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
- Immunohistochemical Expression of p62 in Feline Mammary Carcinoma and Non-Neoplastic Mammary Tissue.Animals : an open access journal from MDPI · 2022Article
- Sequestosome 1/p62: A multitasker in the regulation of malignant tumor aggression (Review).International journal of oncology · 2021Review
- Review
- Autophagy-targeted therapy to modulate age-related diseases: Success, pitfalls, and new directions.Current research in pharmacology and drug discovery · 2021Review
- p62/SQSTM1: 'Jack of all trades' in health and cancer.The FEBS journal · 2019Review
- Functions of autophagy in the tumor microenvironment and cancer metastasis.The FEBS journal · 2018Review
- Cytoplasmic SQSTM1/ P62 Accumulation Predicates a Poor Prognosis in Patients with Malignant Tumor.Journal of Cancer · 2018Article
- Autophagy mediates epithelial cancer chemoresistance by reducing p62/SQSTM1 accumulation.PloS one · 2018Article
- Activation of p62/SQSTM1-Keap1-Nuclear Factor Erythroid 2-Related Factor 2 Pathway in Cancer.Frontiers in oncology · 2018Review
- Autophagy regulates UBC9 levels during viral-mediated tumorigenesis.PLoS pathogens · 2017Article
- p62/SQSTM1-Dr. Jekyll and Mr. Hyde that prevents oxidative stress but promotes liver cancer.FEBS letters · 2016Review
- P62: An emerging oncotarget for osteolytic metastasis.Journal of bone oncology · 2016Review
- RNA-Seq and ChIP-Seq reveal SQSTM1/p62 as a key mediator of JunB suppression of NF-κB-dependent inflammation.The Journal of investigative dermatology · 2015Article
- Mitophagy and cancer.Cancer & metabolism · 2015Article
- HighCancer diagnosis & prognosisArticle
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The phosphoinositol-3 kinase (PI3K) pathway is highly dysregulated in squamous cell carcinoma of the head and neck (SCCHN). While inhibitors of the PI3K/AKT pathway are being developed in cancer, their efficacy does not appear to be related to the presence of mutations or amplification in pathway genes. The PI3K pathway is a major regulator of macro-autophagy, an evolutionarily conserved catabolic process that degrades cellular materials to promote cellular homeostasis and survival under stress. Employing a panel of SCCHN cell lines, we observed a significant correlation between the activity of PI3K/AKT inhibitors and their ability to induce autophagy. More specifically, resistance to these inhibitors was associated with accumulation of p62/SQSTM1, a pleotropic protein that is consumed during autophagy, while loss of autophagy was, for the first time, found to be due to silencing of an essential autophagy gene, ATG7. Moreover, modulating ATG7 and p62/SQSTM1 could regulate sensitivity to PI3K/AKT inhibitors, underscoring a mechanistic link between autophagy and drug sensitivity. Analysis of human tissues revealed progressive accumulation of p62/SQSTM1 in a significant proportion of cancer samples compared to normal tissue, suggesting that defective autophagy has relevance to SCCHN. These findings are further validated by analysis of TCGA data confirming homozygous deletion and mRNA down-regulation of ATG7 in 10.0% of SCCHN samples. Taken together, these data indicate that p62/SQSTM1 levels modulate sensitivity to PI3K/AKT inhibitors; cancers vary in their capacity to undergo autophagy through epigenetic modification and, when deficient, accumulate p62/SQSTM1; and expression of autophagy-related proteins may serve as markers for resistance to PI3K/AKT inhibitors in SCCHN.
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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.