ArticleOncogene2021
Oct4 confers stemness and radioresistance to head and neck squamous cell carcinoma by regulating the homologous recombination factors PSMC3IP and RAD54L.
Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 57 citations in OpenAlex.
- Unraveling the molecular landscape: an overview on gene expression, epigenetic alterations, and therapeutic challenges in head and neck squamous cell carcinoma.Molecular genetics and genomics : MGG · 2026Review
- Loss of WT1 Drives Adaptive Plasticity in CCDC6-RET Selpercatinib-Resistant Papillary Thyroid Cancer.Current issues in molecular biology · 2026Article
- Article
- Gene regulatory network transitions reveal the central transcription factors in lung adenocarcinoma progression.NPJ systems biology and applications · 2026Article
- Cancer stem cell mechanisms and targeted therapeutic strategies in head and neck squamous cell carcinoma.Cancer letters · 2025Review
- Integrative analysis of non-small cell lung cancer identifies Jumonji domain-containing 6/ETS homologous factor axis as a target to overcome radioresistance.Signal transduction and targeted therapy · 2025Article
- MYO1B promotes radioresistance in head and neck squamous cell carcinoma by regulating tumor stemness and DNA damage repair via the PI3K/AKT pathway.Cancer cell international · 2025Article
- Adaptation to Arginine Deprivation Leads to a More Aggressive, Therapy-Resistant Phenotype in HNSCC Cells.Biomolecules · 2025Article
- Multifaceted roles of OCT4 in tumor microenvironment: biology and therapeutic implications.Oncogene · 2025Review
- Dissecting the Impact of Genetic Background on Oncogenic Response to Radiation Exposure in theCells · 2024Article
- Cancer stem cells: advances in knowledge and implications for cancer therapy.Signal transduction and targeted therapy · 2024Review
- Transcriptional regulation of cancer stem cell: regulatory factors elucidation and cancer treatment strategies.Journal of experimental & clinical cancer research : CR · 2024Review
- Oct4 activates IL-17A to orchestrate M2 macrophage polarization and cervical cancer metastasis.Cancer immunology, immunotherapy : CII · 2024Article
- RNA mExperimental & molecular medicine · 2024Article
- SOX2 and OCT4 mediate radiation and drug resistance in pancreatic tumor organoids.Cell death discovery · 2024Article
- Myriad factors and pathways influencing tumor radiotherapy resistance.Open life sciences · 2024Review
- Article
- Immunotargeting of Cancer Stem Cells.Cancers · 2023Review
- CD24+CD44+CD54+EpCAM+ gastric cancer stem cells predict tumor progression and metastasis: clinical and experimental evidence.Stem cell research & therapy · 2023Article
- Oct4 promoted proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in colon cancer cells by activating the SCF/c-Kit signaling pathway.Cell cycle (Georgetown, Tex.) · 2023Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Head and neck squamous cell carcinoma (HNSCC) is often being diagnosed at an advanced stage, conferring a poor prognosis. The probability of local tumor control after radiotherapy depends on the eradication of cancer stem cells (CSCs) with activated DNA repair. This study provides evidence that the CSC-related transcription factor Oct4 contributes to HNSCC radioresistance by regulating DNA damage response and the CSC phenotype. Knockdown of Oct4 A isoform reduced self-renewal capacity in HNSCC and led to partial tumor cell radiosensitization caused by transcriptional downregulation of the cell cycle checkpoint kinases CHK1 and WEE1 and homologous recombination (HR) repair genes PSMC3IP and RAD54L. Besides, PARP inhibition with Olaparib selectively radiosensitized Oct4 A knockout, but not wild-type HNSCC cells. This finding links Oct4 A to the HR-mediated DNA repair mechanisms. In turn, knockdown of PSMC3IP and RAD54L reduced the HNSCC self-renewal capacity and clonogenic cell survival after irradiation, suggesting the interplay between DNA repair and the CSC phenotype. Similar to the effect of Oct4 knockdown, overexpression of Oct4 also resulted in significant HNSCC radiosensitization and increased DNA damage, suggesting that Oct4-dependent regulation of DNA repair depends on its fine-tuned expression. In line with this observation, HNSCC patients with high and low nuclear Oct4 expression at the invasive tumor front exhibited better loco-regional tumor control after postoperative radio(chemo)therapy compared to the intermediate expression subgroup. Thus, we found that the Oct4-driven transcriptional program plays a critical role in regulating HNSCC radioresistance, and a combination of radiotherapy with PARP inhibitors may induce synthetic lethality in Oct4-deregulated tumors.
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