ArticleCell death & disease2020
ERK1/2-Nanog signaling pathway enhances CD44(+) cancer stem-like cell phenotypes and epithelial-to-mesenchymal transition in head and neck squamous cell carcinomas.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 34 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- A Systematic Review to Clarify the Prognostic Values of CD44 and CD44Frontiers in oncology · 2021Pooled it
- Correction: Hsu et al. Hyaluronan: An Architect and Integrator for Cancer and Neural Diseases.International journal of molecular sciences · 2025Article
- Exosomal miR-6126 as a novel therapeutic target for overcoming resistance of anti-cancer effect in hepatocellular carcinoma.BMC cancer · 2024Article
- Retraction: Role of Rac1 Pathway in Epithelial-to-Mesenchymal Transition and Cancer Stem-like Cell Phenotypes in Gastric Adenocarcinoma.Molecular cancer research : MCR · 2024Article
- Retraction: Chemotherapy Resistance in Diffuse-Type Gastric Adenocarcinoma Is Mediated by RhoA Activation in Cancer Stem-Like Cells.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Three-dimensional matrix stiffness modulates mechanosensitive and phenotypic alterations in oral squamous cell carcinoma spheroids.APL bioengineering · 2024Article
- CD44 and its implication in neoplastic diseases.MedComm · 2024Review
- Retraction Note: PIK3R3, part of the regulatory domain of PI3K, is upregulated in sarcoma stem-like cells and promotes invasion, migration, and chemotherapy resistance.Cell death & disease · 2024Article
- SALL4 promotes cancer stem-like cell phenotype and radioresistance in oral squamous cell carcinomas via methyltransferase-like 3-mediated m6A modification.Cell death & disease · 2024Article
- Metronomic and single high-dose paclitaxel treatments produce distinct heterogenous chemoresistant cancer cell populations.Scientific reports · 2023Article
- Targeting cancer stem cells as a strategy for reducing chemotherapy resistance in head and neck cancers.Journal of cancer research and clinical oncology · 2023Review
- The Three-Dimensional In Vitro Cell Culture Models in the Study of Oral Cancer Immune Microenvironment.Cancers · 2023Review
- CD44 Modulates Cell Migration and Invasion in Ewing Sarcoma Cells.International journal of molecular sciences · 2023Article
- The First Crested Duck Genome Reveals Clues to Genetic Compensation and Crest Cushion Formation.Genomics, proteomics & bioinformatics · 2023Article
- Hyaluronan Receptors as Mediators and Modulators of the Tumor Microenvironment.Advanced healthcare materials · 2023Review
- SOX2 promotes a cancer stem cell-like phenotype and local spreading in oral squamous cell carcinoma.PloS one · 2023Article
- Review
- A NANOG-pERK reciprocal regulatory circuit regulates Nanog autoregulation and ERK signaling dynamics.EMBO reports · 2022Article
- Gemcitabine resistance of pancreatic cancer cells is mediated by IGF1R dependent upregulation of CD44 expression and isoform switching.Cell death & disease · 2022Article
- Article
Corrections and comments
- Retraction · 2024-03-15Concerns/Issues about Image · Concerns/Issues about Human Subject Welfare · Duplication of/in Image · Investigation by Journal/Publisher · Investigation by Third Party · Lack of IRB/IACUC Approval and/or Compliance · Original Data and/or Images not Provided and/or not Available · Unreliable Results and/or Conclusions · · See also: https://pubpeer.com/publications/E793A526E0ED16CC5E7561655790F9
- Retracted
Authors and funding
10 authors at 6 institutions in 3 countries.
Funding
Abstract
Head and neck squamous cell carcinomas (HNSCCs) harbor a subset of cells that are CD44(+) and present with malignancy and radiotherapy resistance. As a key regulator of self-renewal, Nanog expression not only determines cell fate in pluripotent cells but also mediates tumorigenesis in cancer cells; thus, we examined the role of Nanog in CD44(+) HNSCC. Three HNSCC cell lines, tumor xenografts, and patient tumors were examined. Nanog levels were significantly higher in CD44(+) HNSCC spheroids than in CD44(-) spheroids, and further increased when grown as spheroids to enrich for CSCs. CD44(+) spheroids showed a 3.4-7.5-fold increase in migration and invasion compared with CD44(-) spheroids and were resistant to radiation therapy, which was reversed by inhibiting Nanog. Nanog knockdown also decreased spheroid formation by 66.5-68.8%. Moreover, a phosphokinase array identified upregulated ERK1/2 signaling in CD44(+) HNSCC cells compared with that in CD44(-) cells. ERK1/2 signaling was found to regulate Nanog expression, aiding tumor progression, metastasis, and radiotherapy resistance. In xenograft models, the combination of radiation and Nanog or ERK1/2 inhibition inhibited tumor growth by 75.6% and 79.1%, respectively. In lung metastasis models, CD44(+) cells injected into the tail vein of mice led to significantly more lung metastases and higher Nanog expression level compared with that by ERK1/2-knockdown CD44(+) cells. Finally, in tumor tissues, CD44 and Nanog expression levels were correlated with tumorigenesis in HNSCC patients. Thus, targeting Nanog and the ERK1/2 signaling pathway may prevent or reverse CSC phenotypes and epithelial-mesenchymal transition that drive tumor progression, metastasis, and radiotherapy resistance in HNSCC.
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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.