title: C-Met/miR-130b axis as novel mechanism and biomarker for castration resistance state acquisition.
abstract: Although a significant subset of prostate tumors remain indolent during the entire life, the advanced forms are still one of the leading cause of cancer-related death. There are not reliable markers distinguishing indolent from aggressive forms. Here we highlighted a new molecular circuitry involving microRNA and coding genes promoting cancer progression and castration resistance. Our preclinical and clinical data demonstrated that c-Met activation increases miR-130b levels, inhibits androgen receptor expression, promotes cancer spreading and resistance to hormone ablation therapy. The relevance of these findings was confirmed on patients' samples and by in silico analysis on an independent patient cohort from Taylor's platform. Data suggest c-Met/miR-130b axis as a new prognostic marker for patients' risk assessment and as an indicator of therapy resistance. Our results propose new biomarkers for therapy decision-making in all phases of the pathology. Data may help identify high-risk patients to be treated with adjuvant therapy together with alternative cure for castration-resistant forms while facilitating the identification of possible patients candidates for anti-Met therapy. In addition, we demonstrated that it is possible to evaluate Met/miR-130b axis expression in exosomes isolated from peripheral blood of surgery candidates and advanced patients offering a new non-invasive tool for active surveillance and therapy monitoring.
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Cannistraci
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.|Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Federici
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Addario
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.|Department of Anatomical, Histological, Forensic &Orthopaedic Sciences, Histology and Medical Embryology Section, Sapienza University of Rome, Rome, Italy.
authors.forename: A L
authors.initials: AL
authors.lastname: Di Pace
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.|Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Grassi
authors.affiliation: Department of Urology, S. Giovanni Bosco Hospital, Turin, Italy.|Department of Urology, Campus Biomedico University, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Muto
authors.affiliation: Department of Urology, S. Giovanni Bosco Hospital, Turin, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Collura
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: M
authors.identifier: 0000-0002-0262-842X
authors.initials: M
authors.lastname: Signore
authors.affiliation: Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: L
authors.initials: L
authors.lastname: De Salvo
authors.affiliation: Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Sentinelli
authors.affiliation: Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: G
authors.identifier: 0000-0002-4868-9025
authors.initials: G
authors.lastname: Simone
authors.affiliation: Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Costantini
authors.affiliation: Institute of Medical Pathology, Università Cattolica, Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Nanni
authors.affiliation: National Research Council (CNR), Institute of Cell Biology and Neurobiology, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Farsetti
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Coppola
authors.affiliation: Institute of General Pathology, Università Cattolica and Policlinico Gemelli, Rome, Italy.
authors.forename: R
authors.initials: R
authors.lastname: De Maria
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.|Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Bonci
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D018450:Disease Progression; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D064129:Prostatic Neoplasms, Castration-Resistant / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C554019:MIRN130 microRNA, human; D035683:MicroRNAs; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met