Serrano, Maria JOrtega, Francisco GAlvarez-Cubero, Maria JNadal, RosaSanchez-Rovira, PedroSalido, MartaRodríguez, MaríaGarcía-Puche, Jose LDelgado-Rodriguez, MiguelSolé, FranciscoGarcía, Maria APerán, MacarenaRosell, RafaelMarchal, Juan ALorente, Jose A2016-05-052016-05-052014-09-15Serrano MJ, Ortega FG, Alvarez-Cubero MJ, Nadal R, Sanchez-Rovira P, Salido M, et al. EMT and EGFR in CTCs cytokeratin negative non-metastatic breast cancer. Oncotarget. 2014 ; 5(17):7486-97http://hdl.handle.net/10668/2183Journal Article; Research Support, Non-U.S. Gov't;Circulating tumor cells (CTCs) are frequently associated with epithelial-mesenchymal transition (EMT).The objective of this study was to detect EMT phenotype through Vimentin (VIM) and Slug expression in cytokeratin (CK)-negative CTCs in non-metastatic breast cancer patients and to determine the importance of EGFR in the EMT phenomenon. In CK-negative CTCs samples, both VIM and Slug markers were co-expressed in the most of patients. Among patients EGFR+, half of them were positive for these EMT markers. Furthermore, after a systemic treatment 68% of patients switched from CK- to CK+ CTCs. In our experimental model we found that activation of EGFR signaling by its ligand on MCF-7 cells is sufficient to increase EMT phenotypes, to inhibit apoptotic events and to induce the loss of CK expression. The simultaneous detection of both EGFR and EMT markers in CTCs may improve prognostic or predictive information in patients with operable breast cancer.enBreast CancerCirculating Tumor CellsEGFREpithelial-Mesenchymal TransitionVimentinSlugBcl-2ApoptosisNeoplasias de la mamaTransición epitelial-mesenquimalGastrópodosAnimalesFilamentos intermediosQueratinasLínea celular tumoralModelos teóricosCélulas neoplásicas circulantesFenotipoPronósticoMarcadores biológicos de tumorHumanosVimentinaMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Breast NeoplasmsMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Transdifferentiation::Epithelial-Mesenchymal TransitionMedical Subject Headings::Organisms::Eukaryota::Animals::Invertebrates::Mollusca::GastropodaMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::Cytoskeleton::Intermediate FilamentsMedical Subject Headings::Chemicals and Drugs::Macromolecular Substances::Polymers::Biopolymers::Intermediate Filament Proteins::KeratinsMedical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, TumorMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, TheoreticalMedical Subject Headings::Anatomy::Cells::Neoplastic Cells, CirculatingMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::PhenotypeMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::PrognosisMedical Subject Headings::Chemicals and Drugs::Biological Factors::Biological Markers::Tumor Markers, BiologicalMedicjavascript:void(null);al Subject Headings::Chemicals and Drugs::Macromolecular Substances::Polymers::Biopolymers::Intermediate Filament Proteins::VimentinMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Chemicals and Drugs::Macromolecular Substances::Polymers::Biopolymers::Intermediate Filament Proteins::KeratinsMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Microscopy::Microscopy, ConfocalMedical Subject Headings::Named Groups::Persons::Age Groups::Adult::Middle AgedMedical Subject Headings::Diseases::Neoplasms::Neoplastic Processes::Neoplasm Metastasis::Neoplastic Cells, CirculatingMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Nucleic Acid Amplification Techniques::Polymerase Chain Reaction::Real-Time Polymerase Chain ReactionMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Peptide::Receptors, Growth Factor::Receptor, Epidermal Growth FactorMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Transcription FactorsMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Cytoskeletal Proteins::Intermediate Filament Proteins::Vimentinresearch article25277187open access10.18632/oncotarget.22171949-2553PMC4202138