ArticleOncogene2022
Autophagy regulates the cancer stem cell phenotype of head and neck squamous cell carcinoma through the noncanonical FOXO3/SOX2 axis.
Article in Oncogene, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 40 citations in OpenAlex.
- Translational insights and clinical challenges of targeting cancer stem cells.Signal transduction and targeted therapy · 2026Review
- Role of autophagy in tumorigenesis and drug resistance: molecular mechanisms and therapeutic targets.Molecular biomedicine · 2026Review
- Targeting the LHX1-LDB1 Complex Restores STING-dependent Senescence Surveillance and Inhibits Head and Neck Cancer Progression.International journal of biological sciences · 2026Article
- TPX2-mediated autophagy maintains cancer stemness in LUAD: bioinformatic screening and functional validation.Frontiers in oncology · 2026Article
- E2F1-autophagy-ALDH1A1 axis enhances self-renewal and drug resistance of lung cancer stem-like cells in a p53-dependent manner.Journal of experimental & clinical cancer research : CR · 2025Article
- TBK1 is a signaling hub in coordinating stress-adaptive mechanisms in head and neck cancer progression.Autophagy · 2025Article
- Cancer stem cells: Bridging microenvironmental interactions and clinical therapy.Clinical and translational medicine · 2025Review
- Article
- The dual role of autophagy in cancer stem cells: implications for tumor progression and therapy resistance.Journal of translational medicine · 2025Review
- ATP6V1D drives hepatocellular carcinoma stemness and progression via both lysosome acidification-dependent and -independent mechanisms.Autophagy · 2025Article
- Betaine inhibits the stem cell-like properties of hepatocellular carcinoma by activating autophagy via SAM/mTheranostics · 2025Article
- Propofol reduces breast cancer cell stemness via FOXO3/SOX2 axis.Journal of Cancer · 2025Article
- CAFs-derived lactate enhances the cancer stemness through inhibiting the MST1 ubiquitination degradation in OSCC.Cell & bioscience · 2024Article
- Dysregulated Wnt/β-catenin signaling confers resistance to cuproptosis in cancer cells.Cell death and differentiation · 2024Article
- Cleistanthin A derivative disrupts autophagy and suppresses head and neck squamous cell carcinoma progression via targeted vacuolar ATPase.Scientific reports · 2024Article
- Is Autophagy Targeting a Valid Adjuvant Strategy in Conjunction with Tyrosine Kinase Inhibitors?Cancers · 2024Review
- Protein homeostasis maintained by HOOK1 levels promotes the tumorigenic and stemness properties of ovarian cancer cells through reticulum stress and autophagy.Journal of experimental & clinical cancer research : CR · 2024Article
- HDAC9 and miR-512 Regulate CAGE-Promoted Anti-Cancer Drug Resistance and Cellular Proliferation.Current issues in molecular biology · 2024Article
- Contribution of Autophagy to Epithelial Mesenchymal Transition Induction during Cancer Progression.Cancers · 2024Review
- Mitophagy-Mediated Tumor Dormancy Protects Cancer Cells from Chemotherapy.Biomedicines · 2024Article
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
Autophagy is an essential catabolic process that orchestrates cellular homeostasis and plays dual roles in tumor promotion and suppression. However, the mechanism by which autophagy affects the self-renewal of cancer stem cells (CSCs) remains unclear. In this study, we investigated whether autophagy activation contributes to CSC properties of head and neck squamous cell carcinoma (HNSCC). The results showed that the autophagy level and CSC properties of HNSCC cells were elevated in response to several adverse conditions, including treatment with cisplatin, starvation, and hypoxia. Pretreatment with autophagy inhibitors, such as 3-MA and chloroquine, diminished the CSC properties acquired under adverse conditions. In addition, the isolated CSCs were endowed with stronger autophagic activity than non-CSCs, and the CSC properties were dampened when autophagy was inhibited either by 3-MA, chloroquine, or Beclin1 knockdown. Notably, the tumor-initiating activity of CSCs was decreased upon knocking down Beclin1. Further study revealed that FOXO3, a substrate for autophagy, was enriched in the nucleus of cells with lower autophagy levels. Nuclear FOXO3 directly bound to the promoter region of SOX2 and negatively regulated its transcriptional activity. Overexpression of FOXO3 decreased the expression of SOX2 and thereby impaired the CSC phenotype both in vitro and in vivo. Taken together, our findings suggest that the activation of autophagy is essential for the acquisition of CSC properties in adverse conditions and the self-renewal of CSCs. We clarify the role of autophagy in regulating the CSC phenotype and demonstrate that the noncanonical FOXO3/SOX2 axis is the intrinsic regulatory mechanism.
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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 Socratic graph.