Oncotarget

Research Papers:

PATZ1 acts as a tumor suppressor in thyroid cancer via targeting p53-dependent genes involved in EMT and cell migration

Gennaro Chiappetta _, Teresa Valentino, Michela Vitiello, Rosa Pasquinelli, Mario Monaco, Giuseppe Palma, Romina Sepe, Antonio Luciano, Pierlorenzo Pallante, Dario Palmieri, Concetta Aiello, Domenica Rea, Simona Nunzia Losito, Claudio Arra, Alfredo Fusco and Monica Fedele

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Oncotarget. 2015; 6:5310-5323. https://doi.org/10.18632/oncotarget.2776

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Abstract

Gennaro Chiappetta1,*, Teresa Valentino2,*, Michela Vitiello2, Rosa Pasquinelli1, Mario Monaco1, Giuseppe Palma3, Romina Sepe2,4, Antonio Luciano3, Pierlorenzo Pallante2, Dario Palmieri5, Concetta Aiello1, Domenica Rea3, Simona Nunzia Losito1, Claudio Arra3, Alfredo Fusco2,4, Monica Fedele2

1Department of Experimental Oncology, Functional Genomic Unit, National Cancer Institute “Fondazione Giovanni Pascale”, IRCCS, 80131 Naples, Italy

2Institute of Experimental Endocrinology and Oncology (IEOS), National Research Counsil (CNR), 80131 Naples, Italy

3Animal Facility, National Cancer Institute “Fondazione Giovanni Pascale”, IRCCS, 80131 Naples, Italy

4Department of Molecular Medicine and Medical Biotechnologies, University of Naples “Federico II”, 80131 Naples, Italy

5Departments of Molecular Virology, Immunology and Human Genetics, Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, USA

*These authors have contributed equally to this work

Correspondence to:

Monica Fedele, e-mail: mfedele@unina.it

Gennaro Chiappetta, e-mail: g.chiappetta@istitutotumori.na.it

Keywords: thyroid cancer, PATZ1, Epithelial-Mesenchymal Transition, cell migration

Received: July 22, 2014     Accepted: November 18, 2014     Published: December 16, 2014

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.


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