ArticlePloS one2012
Analysis of marker-defined HNSCC subpopulations reveals a dynamic regulation of tumor initiating properties.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- Regulated cell death plasticity in cancer: thresholds, reversibility, and therapeutic failure.Journal of translational medicine · 2026Review
- From Worms to Tumors: Conserved Strategies of Cellular Arrest and Survival Governing Dormancy.Cancer research · 2025Review
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- In vivo production of fluorine-18 in a chicken egg tumor model of breast cancer for proton therapy range verification.Scientific reports · 2022Article
- Tumor dormancy in bone.Cancer reports (Hoboken, N.J.) · 2020Review
- Stem Cell Plasticity and Dormancy in the Development of Cancer Therapy Resistance.Frontiers in oncology · 2019Review
- TGF-β-Induced Quiescence Mediates Chemoresistance of Tumor-Propagating Cells in Squamous Cell Carcinoma.Cell stem cell · 2017Article
- Establishment of oral squamous cell carcinoma cell line and magnetic bead-based isolation and characterization of its CD90/CD44 subpopulations.Oncotarget · 2017Article
- RGD-Binding Integrins in Head and Neck Cancers.Cancers · 2017Review
- Article
- Cancer stem cell related markers of radioresistance in head and neck squamous cell carcinoma.Oncotarget · 2015Article
- Mutation and Transcriptional Profiling of Formalin-Fixed Paraffin Embedded Specimens as Companion Methods to Immunohistochemistry for Determining Therapeutic Targets in Oropharyngeal Squamous Cell Carcinoma (OPSCC): A Pilot of Proof of Principle.Head and neck pathology · 2015Article
- Wnt signaling regulation of stem-like properties in human lung adenocarcinoma cell lines.Medical oncology (Northwood, London, England) · 2015Article
- NR2F1 controls tumour cell dormancy via SOX9- and RARβ-driven quiescence programmes.Nature communications · 2015Article
- Mechanisms of disseminated cancer cell dormancy: an awakening field.Nature reviews. Cancer · 2014Review
- Melanoma stem cells and metastasis: mimicking hematopoietic cell trafficking?Laboratory investigation; a journal of technical methods and pathology · 2014Review
- Article
- A new gamboge derivative compound 2 inhibits cancer stem-like cells via suppressing EGFR tyrosine phosphorylation in head and neck squamous cell carcinoma.Journal of cellular and molecular medicine · 2013Article
- Inactivation of the mTORC1-eukaryotic translation initiation factor 4E pathway alters stress granule formation.Molecular and cellular biology · 2013Article
- From single cells to deep phenotypes in cancer.Nature biotechnology · 2012Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Head and neck squamous carcinoma (HNSCC) tumors carry dismal long-term prognosis and the role of tumor initiating cells (TICs) in this cancer is unclear. We investigated in HNSCC xenografts whether specific tumor subpopulations contributed to tumor growth. We used a CFSE-based label retentions assay, CD49f (α6-integrin) surface levels and aldehyde dehydrogenase (ALDH) activity to profile HNSCC subpopulations. The tumorigenic potential of marker-positive and -negative subpopulations was tested in nude (Balb/c nu/nu) and NSG (NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl)/SzJ) mice and chicken embryo chorioallantoic membrane (CAM) assays. Here we identified in HEp3, SQ20b and FaDu HNSCC xenografts a subpopulation of G0/G1-arrested slow-cycling CD49f(high)/ALDH1A1(high)/H3K4/K27me3(low) subpopulation (CD49f+) of tumor cells. A strikingly similar CD49f(high)/H3K27me3(low) subpopulation is also present in primary human HNSCC tumors and metastases. While only sorted CD49f(high)/ALDH(high), label retaining cells (LRC) proliferated immediately in vivo, with time the CD49f(low)/ALDH(low), non-LRC (NLRC) tumor cell subpopulations were also able to regain tumorigenic capacity; this was linked to restoration of CD49f(high)/ALDH(high), label retaining cells. In addition, CD49f is required for HEp3 cell tumorigenicity and to maintain low levels of H3K4/K27me3. CD49f+ cells also displayed reduced expression of the histone-lysine N-methyltransferase EZH2 and ERK1/2 phosphorylation. This suggests that although transiently quiescent, their unique chromatin structure is poised for rapid transcriptional activation. CD49f- cells can "reprogram" and also achieve this state eventually. We propose that in HNSCC tumors, epigenetic mechanisms likely driven by CD49f signaling dynamically regulate HNSCC xenograft phenotypic heterogeneity. This allows multiple tumor cell subpopulations to drive tumor growth suggesting that their dynamic nature renders them a "moving target" and their eradication might require more persistent strategies.
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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.