title: EMT and EGFR in CTCs cytokeratin negative non-metastatic breast cancer.
abstract: 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.
authors.affiliation: GENYO. Pfizer-University of Granada-Andalusian Government Centre of Genomics and Oncology, Granada, Spain. Laboratory of Genetic Identification-UGR, Department of Legal Medicine, University of Granada, Granada, Spain. Contributed equally to this work.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Serrano
authors.affiliation: GENYO. Pfizer-University of Granada-Andalusian Government Centre of Genomics and Oncology, Granada, Spain. Contributed equally to this work.
authors.forename: Francisco G
authors.initials: FG
authors.lastname: Ortega
authors.affiliation: GENYO. Pfizer-University of Granada-Andalusian Government Centre of Genomics and Oncology, Granada, Spain. Laboratory of Genetic Identification-UGR, Department of Legal Medicine, University of Granada, Granada, Spain.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Alvarez-Cubero
authors.affiliation: Hospital de Barcelona, Medical Oncology Department, Barcelona, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Nadal
authors.affiliation: University of Jaén, Division of Preventive Medicine and Public Health, CIBERESP, Jaén, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Sanchez-Rovira
authors.affiliation: Molecular Cytogenetics Laboratory; Pathology Department, Parc de Salut Mar-Hospital del Mar-IMIM-GRETNHE, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Salido
authors.affiliation: Molecular Cytogenetics Laboratory; Pathology Department, Parc de Salut Mar-Hospital del Mar-IMIM-GRETNHE, Barcelona, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Rodríguez
authors.affiliation: GENYO. Pfizer-University of Granada-Andalusian Government Centre of Genomics and Oncology, Granada, Spain.
authors.forename: Jose L
authors.initials: JL
authors.lastname: García-Puche
authors.affiliation: University of Jaén, Division of Preventive Medicine and Public Health, CIBERESP, Jaén, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Delgado-Rodriguez
authors.affiliation: Medicine Department. Universitat Autònoma de Barcelona, Barcelona, Spain. Institut de Recerca contra la Leucèmia Josep Carreras, Badalona, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Solé
authors.affiliation: Department of Oncology, Virgen de las Nieves, University Hospital, Granada, Spain.
authors.forename: Maria A
authors.initials: MA
authors.lastname: García
authors.affiliation: University of Jaén, Division of Preventive Medicine and Public Health, CIBERESP, Jaén, Spain. Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research, University of Granada, Granada, Spain.
authors.forename: Macarena
authors.initials: M
authors.lastname: Perán
authors.affiliation: Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain (RR); Pangaea Biotech SL, USP Dexeus University Institute, Barcelona, Spain (RR, MAM).
authors.forename: Rafael
authors.initials: R
authors.lastname: Rosell
authors.affiliation: Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research, University of Granada, Granada, Spain. Department of Human Anatomy and Embryology, University of Granada, Granada, Spain.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Marchal
authors.affiliation: GENYO. Pfizer-University of Granada-Andalusian Government Centre of Genomics and Oncology, Granada, Spain. Laboratory of Genetic Identification-UGR, Department of Legal Medicine, University of Granada, Granada, Spain.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Lorente
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D066246:ErbB Receptors / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007633:Keratins / Q000096:biosynthesis; D061986:MCF-7 Cells; D018613:Microscopy, Confocal; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000032:analysis / Q000096:biosynthesis; D014746:Vimentin / Q000032:analysis / Q000096:biosynthesis
chemical_list: D014408:Biomarkers, Tumor; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D014746:Vimentin; D007633:Keratins; C512478:EGFR protein, human; D066246:ErbB Receptors