Descripción del proyecto
TUMOR GROWTH AND METASTATIC DISSEMINATION RELY ON RARE CANCER STEM CELLS, SUPERIMPOSED UPON ONCOGENIC DRIVER MUTATIONS, EVIDENCES ARE MOUNTING FOR EPIGENETIC GENE REPROGRAMMING AS A MAJOR MODE USED BY CANCER CELLS FOR THEIR MAINTENANCE AND MALIGNANT PROGRESSION, RECENT EVIDENCE POINTS TO A CRITICAL REGULATORY ROLE PLAYED BY EPIGENETIC CUES THAT INCLUDE NON-CODING RNAS (NCRNAS) TO DRIVE THE TRANSITION OF CANCER CELLS TO METASTATIC CANCER STEM CELLS (MCSCS), WE PROPOSE THAT EPIGENETIC CUES, IN PARTICULAR DICTATED BY DYSREGULATED SPECIFIC MICRORNAS AND OTHER NCRNAS, PLAY KEY ROLES IN THE EMERGENCE OF MCSCS, WE WILL USE MCF10 BREAST EPITHELIAL CELL-DERIVED MODELS TO SCREEN FOR NCRNAS THAT CONFER THESE CELLS WITH ENHANCED MAMMOSPHERE GROWTH AS A SURROGATE ASSAY FOR THE ACQUISITION OF SELF-RENEWAL PROPERTIES, THIS IS A NEW APPROACH TO SCREEN FOR AND IDENTIFY NCRNAS THAT MAY POTENTIATE OR ENABLE CELL SELF-RENEWAL, GENES AND NCRNAS THUS CHARACTERIZED WILL BE TESTED FOR THEIR CAPACITY TO MODULATE THE GROWTH, TUMORIGENIC AND METASTATIC POTENTIALS OF MODEL BREAST CANCER CELLS, IN VITRO AND IN VIVO, WE WILL VALIDATE OUR RESULTS IN HUMAN BREAST CARCINOMA SAMPLES AT THE GENOMIC, TRANSCRIPTOMIC AND PROTEIN LEVEL IN SERIES OF BREAST TUMOURS WITH DIFFERENT HISTOLOGIES INCLUDING THE INTRIGUING METAPLASTIC CARCINOMAS, FINALLY, WE WILL EXPLORE THE POSSIBLE USE OF NCRNA EVALUATION IN BLOOD SAMPLES AS A CLINICALLY RELEVANT STAGING BIOMARKER IN BREAST CANCER, CANCER\METASTASIS\NCRNAS\CANCER STEM CELLS\HETEROGENEIDAD INTRATUMORAL\CARCINOMA METAPLASICO\DESCUBRIMIENTO DE FARMACOS