ArticleStem cells translational medicine2014
Targeting cancer stem cell plasticity through modulation of epidermal growth factor and insulin-like growth factor receptor signaling in head and neck squamous cell cancer.
Article in Stem cells translational medicine, 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, 33 citations in OpenAlex.
- Convergent adaptive architectures linking chemoresistance and radioresistance in chemoradiotherapy: a systems-level perspective.Frontiers in oncology · 2026Review
- CAN-Scan: A multi-omic phenotype-driven precision oncology platform identifies prognostic biomarkers of therapy response for colorectal cancer.Cell reports. Medicine · 2025Article
- The role of IGF/IGF-1R signaling in the regulation of cancer stem cells.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Review
- Developments and future prospects of personalized medicine in head and neck squamous cell carcinoma diagnoses and treatments.Cancer reports (Hoboken, N.J.) · 2024Review
- Single cell analysis in head and neck cancer reveals potential immune evasion mechanisms during early metastasis.Nature communications · 2023Article
- CAR-T cells targeting HLA-G as potent therapeutic strategy for EGFR-mutated and overexpressed oral cancer.iScience · 2023Article
- Cancer stem cells of head and neck squamous cell carcinoma; distance towards clinical application; a systematic review of literature.American journal of cancer research · 2023Review
- Therapeutic Targeting of Cancer Stem Cells in Lung, Head and Neck, and Bladder Cancers.Cancers · 2021Review
- Review
- Anti-EGFR treatment effects on laryngeal cancer stem cells.American journal of translational research · 2021Article
- Advancement in Cancer Stem Cell Biology and Precision Medicine-Review Article Head and Neck Cancer Stem Cell Plasticity and the Tumor Microenvironment.Frontiers in cell and developmental biology · 2021Review
- Ex Vivo Culture Models to Indicate Therapy Response in Head and Neck Squamous Cell Carcinoma.Cells · 2020Review
- Cancer stem cells-driven tumor growth and immune escape: the Janus face of neurotrophins.Aging · 2019Article
- Epidermal Growth Factor (EGF) Autocrine Activation of Human Platelets Promotes EGF Receptor-Dependent Oral Squamous Cell Carcinoma Invasion, Migration, and Epithelial Mesenchymal Transition.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- GNA13 expression promotes drug resistance and tumor-initiating phenotypes in squamous cell cancers.Oncogene · 2018Article
- Long noncoding RNA EGFR-AS1 mediates epidermal growth factor receptor addiction and modulates treatment response in squamous cell carcinoma.Nature medicine · 2017Article
- Metalloprotease-disintegrin ADAM12 actively promotes the stem cell-like phenotype in claudin-low breast cancer.Molecular cancer · 2017Article
- Feasibility of Primary Tumor Culture Models and Preclinical Prediction Assays for Head and Neck Cancer: A Narrative Review.Cancers · 2015Review
- Paracrine factors of human fetal MSCs inhibit liver cancer growth through reduced activation of IGF-1R/PI3K/Akt signaling.Molecular therapy : the journal of the American Society of Gene Therapy · 2015Article
- Article
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
Emerging data suggest that cancer stem cells (CSCs) exist in equilibrium with differentiated cells and that stochastic transitions between these states can account for tumor heterogeneity and drug resistance. The aim of this study was to establish an in vitro system that recapitulates stem cell plasticity in head and neck squamous cell cancers (HNSCCs) and identify the factors that play a role in the maintenance and repopulation of CSCs. Tumor spheres were established using patient-derived cell lines via anchorage-independent cell culture techniques. These tumor spheres were found to have higher aldehyde dehydrogenase (ALD) cell fractions and increased expression of Kruppel-like factor 4, SRY (sex determining region Y)-box 2, and Nanog and were resistant to γ-radiation, 5-fluorouracil, cisplatin, and etoposide treatment compared with monolayer culture cells. Monolayer cultures were subject to single cell cloning to generate clones with high and low ALD fractions. ALDHigh clones showed higher expression of stem cell and epithelial-mesenchymal transition markers compared with ALDLow clones. ALD fractions, representing stem cell fractions, fluctuated with serial passaging, equilibrating at a level specific to each cell line, and could be augmented by the addition of epidermal growth factor (EGF) and/or insulin. ALDHigh clones showed increased EGF receptor (EGFR) and insulin-like growth factor-1 receptor (IGF-1R) phosphorylation, with increased activation of downstream pathways compared with ALDLow clones. Importantly, blocking these pathways using specific inhibitors against EGFR and IGF-1R reduced stem cell fractions drastically. Taken together, these results show that HNSCC CSCs exhibit plasticity, with the maintenance of the stem cell fraction dependent on the EGFR and IGF-1R pathways and potentially amenable to targeted therapeutics.
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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.