title: PATZ1 acts as a tumor suppressor in thyroid cancer via targeting p53-dependent genes involved in EMT and cell migration.
abstract: PATZ1, a POZ-Zinc finger protein, is emerging as an important regulator of development and cancer, but its cancer-related function as oncogene or tumor-suppressor is still debated. Here, we investigated its possible role in thyroid carcinogenesis. We demonstrated PATZ1 is down-regulated in thyroid carcinomas compared to normal thyroid tissues, with an inverse correlation to the degree of cell differentiation. In fact, PATZ1 expression was significantly further down-regulated in poorly differentiated and anaplastic thyroid cancers compared to the papillary histotype, and it resulted increasingly delocalized from the nucleus to the cytoplasm proceeding from differentiated to undifferentiated thyroid carcinomas. Restoration of PATZ1 expression in three thyroid cancer-derived cell lines, all characterized by fully dedifferentiated cells, significantly inhibited their malignant behaviors, including in vitro proliferation, anchorage-independent growth, migration and invasion, as well as in vivo tumor growth. Consistent with recent studies showing a role for PATZ1 in the p53 pathway, we showed that ectopic expression of PATZ1 in thyroid cancer cells activates p53-dependent pathways opposing epithelial-mesenchymal transition and cell migration to prevent invasiveness. These results provide insights into a potential tumor-suppressor role of PATZ1 in thyroid cancer progression, and thus may have potential clinical relevance for the prognosis and therapy of thyroid cancer.
authors.affiliation: Department of Experimental Oncology, Functional Genomic Unit, National Cancer Institute "Fondazione Giovanni Pascale", IRCCS, 80131 Naples, Italy.
authors.forename: Gennaro
authors.initials: G
authors.lastname: Chiappetta
authors.affiliation: Institute of Experimental Endocrinology and Oncology (IEOS), National Research Counsil (CNR), 80131 Naples, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Valentino
authors.affiliation: Institute of Experimental Endocrinology and Oncology (IEOS), National Research Counsil (CNR), 80131 Naples, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Vitiello
authors.affiliation: Department of Experimental Oncology, Functional Genomic Unit, National Cancer Institute "Fondazione Giovanni Pascale", IRCCS, 80131 Naples, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Pasquinelli
authors.affiliation: Department of Experimental Oncology, Functional Genomic Unit, National Cancer Institute "Fondazione Giovanni Pascale", IRCCS, 80131 Naples, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Monaco
authors.affiliation: Animal Facility, National Cancer Institute "Fondazione Giovanni Pascale", IRCCS, 80131 Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palma
authors.affiliation: Institute of Experimental Endocrinology and Oncology (IEOS), National Research Counsil (CNR), 80131 Naples, Italy.|Department of Molecular Medicine and Medical Biotechnologies, University of Naples "Federico II", 80131 Naples, Italy.
authors.forename: Romina
authors.initials: R
authors.lastname: Sepe
authors.affiliation: Animal Facility, National Cancer Institute "Fondazione Giovanni Pascale", IRCCS, 80131 Naples, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Luciano
authors.affiliation: Institute of Experimental Endocrinology and Oncology (IEOS), National Research Counsil (CNR), 80131 Naples, Italy.
authors.forename: Pierlorenzo
authors.initials: P
authors.lastname: Pallante
authors.affiliation: Departments of Molecular Virology, Immunology and Human Genetics, Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, USA.
authors.forename: Dario
authors.initials: D
authors.lastname: Palmieri
authors.affiliation: Department of Experimental Oncology, Functional Genomic Unit, National Cancer Institute "Fondazione Giovanni Pascale", IRCCS, 80131 Naples, Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: Aiello
authors.affiliation: Animal Facility, National Cancer Institute "Fondazione Giovanni Pascale", IRCCS, 80131 Naples, Italy.
authors.forename: Domenica
authors.initials: D
authors.lastname: Rea
authors.affiliation: Department of Experimental Oncology, Functional Genomic Unit, National Cancer Institute "Fondazione Giovanni Pascale", IRCCS, 80131 Naples, Italy.
authors.forename: Simona Nunzia
authors.initials: SN
authors.lastname: Losito
authors.affiliation: Animal Facility, National Cancer Institute "Fondazione Giovanni Pascale", IRCCS, 80131 Naples, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Arra
authors.affiliation: Institute of Experimental Endocrinology and Oncology (IEOS), National Research Counsil (CNR), 80131 Naples, Italy.|Department of Molecular Medicine and Medical Biotechnologies, University of Naples "Federico II", 80131 Naples, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Fusco
authors.affiliation: Institute of Experimental Endocrinology and Oncology (IEOS), National Research Counsil (CNR), 80131 Naples, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Fedele
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D007124:Immunoenzyme Techniques; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015843:Serpins / Q000235:genetics / Q000378:metabolism; D065646:Thyroid Carcinoma, Anaplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D013961:Thyroid Gland / Q000378:metabolism / Q000473:pathology; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D051741:Kruppel-Like Transcription Factors; C412784:PATZ1 protein, human; D012333:RNA, Messenger; D012097:Repressor Proteins; C516148:SERPINA3 protein, human; D015843:Serpins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: PATZ1; cell migration; epithelial-mesenchymal transition; thyroid cancer