ArticleMolecular cancer therapeutics2013
EGFR inhibition promotes an aggressive invasion pattern mediated by mesenchymal-like tumor cells within squamous cell carcinomas.
Article in Molecular cancer therapeutics, 2013. 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, 27 citations in OpenAlex.
- Cetuximab promotes epithelial to mesenchymal transition and cancer associated fibroblasts in patients with head and neck cancer.Oncotarget · 2015Trial
- How to Achieve Therapeutic Response in Erlotinib-Resistant Head and Neck Squamous Cell Carcinoma? New Insights from Stable Isotope Labeling with Amino Acids in Cell Culture-Based Quantitative Tyrosine Phosphoproteomics.Omics : a journal of integrative biology · 2021Article
- Therapeutic Targeting of Nemo-like Kinase in Primary and Acquired Endocrine-resistant Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Therapeutic role of recurrent ESR1-CCDC170 gene fusions in breast cancer endocrine resistance.Breast cancer research : BCR · 2020Article
- Integrated single-cell and bulk gene expression and ATAC-seq reveals heterogeneity and early changes in pathways associated with resistance to cetuximab in HNSCC-sensitive cell lines.British journal of cancer · 2020Article
- Downregulation of Epidermal Growth Factor Receptor in hepatocellular carcinoma facilitates Transforming Growth Factor-β-induced epithelial to amoeboid transition.Cancer letters · 2019Article
- IL-6 Mediates Cross-Talk between Tumor Cells and Activated Fibroblasts in the Tumor Microenvironment.Cancer research · 2018Article
- Histological transformation after acquired resistance to epidermal growth factor tyrosine kinase inhibitors.International journal of clinical oncology · 2018Review
- Barriers to generating PDX models of HPV-related head and neck cancer.The Laryngoscope · 2017Article
- Interplay between Notch1 and Notch3 promotes EMT and tumor initiation in squamous cell carcinoma.Nature communications · 2017Article
- Embedded Spheroids as Models of the Cancer Microenvironment.Advanced biosystems · 2017Article
- An autophagy-driven pathway of ATP secretion supports the aggressive phenotype of BRAFAutophagy · 2017Article
- Modeling Esophagitis Using Human Three-Dimensional Organotypic Culture System.The American journal of pathology · 2017Article
- Hepatocyte Growth Factor/c-Met Signaling in Head and Neck Cancer and Implications for Treatment.Cancers · 2017Review
- JARID1B Enables Transit between Distinct States of the Stem-like Cell Population in Oral Cancers.Cancer research · 2016Article
- The protective effect of p16(INK4a) in oral cavity carcinomas: p16(Ink4A) dampens tumor invasion-integrated analysis of expression and kinomics pathways.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2015Article
- Tumor and stromal-based contributions to head and neck squamous cell carcinoma invasion.Cancers · 2015Review
- Establishment and characterization of cetuximab resistant head and neck squamous cell carcinoma cell lines: focus on the contribution of the AP-1 transcription factor.American journal of cancer research · 2015Article
- EGFR inhibitors prevent induction of cancer stem-like cells in esophageal squamous cell carcinoma by suppressing epithelial-mesenchymal transition.Cancer biology & therapy · 2015Article
- Phase I study of icotinib, an EGFR tyrosine kinase inhibitor combined with IMRT in nasopharyngeal carcinoma.International journal of clinical and experimental medicine · 2015Article
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
Squamous cell carcinomas (SCC) with an infiltrative invasion pattern carry a higher risk of treatment failure. Such infiltrative invasion may be mediated by a mesenchymal-like subpopulation of malignant cells that we have previously shown to arise from epithelial-mesenchymal transition (EMT) and resist epidermal growth factor receptor (EGFR) targeting. Here, we show that SCCs with infiltrative, high-risk invasion patterns contain abundant mesenchymal-like cells, which are rare in tumors with low-risk patterns. This cellular heterogeneity was modeled accurately in three-dimensional culture using collagen-embedded SCC spheroids, which revealed distinct invasive fronts created by collective migration of E-cadherin-positive cells versus infiltrative migration of individual mesenchymal-like cells. Because EGFR expression by mesenchymal-like cells was diminished in the spheroid model and in human SCCs, we hypothesized that SCCs shift toward infiltrative invasion mediated by this subpopulation during anti-EGFR therapy. Anti-EGFR treatment of spheroids using erlotinib or cetuximab enhanced infiltrative invasion by targeting collective migration by E-cadherin-positive cells while sparing mesenchymal-like cells; by contrast, spheroid invasion in absence of mesenchymal-like cells was abrogated by erlotinib. Similarly, cetuximab treatment of xenografts containing mesenchymal-like cells created an infiltrative invasive front composed of this subpopulation, whereas no such shift was observed upon treating xenografts lacking these cells. These results implicate mesenchymal-like SCC cells as key mediators of the infiltrative invasion seen in tumors with locally aggressive behavior. They further show that EGFR inhibition can promote an infiltrative invasion front composed of mesenchymal-like cells preferentially in tumors where they are abundant before therapy.
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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 OpenQuestion graph.