TY - JOUR
T1 - PATZ1 acts as a tumor suppressor in thyroid cancer via targeting p53-dependent genes involved in EMT and cell migration
AU - Chiappetta, Gennaro
AU - Valentino, Teresa
AU - Vitiello, Michela
AU - Pasquinelli, Rosa
AU - Monaco, Mario
AU - Palma, Giuseppe
AU - Sepe, Romina
AU - Luciano, Antonio
AU - Pallante, Pierlorenzo
AU - Palmieri, Dario
AU - Aiello, Concetta
AU - Rea, Domenica
AU - Losito, Simona Nunzia
AU - Arra, Claudio
AU - Fusco, Alfredo
AU - Fedele, Monica
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - Cell migration
KW - Epithelial-Mesenchymal Transition
KW - PATZ1
KW - Thyroid cancer
UR - http://www.scopus.com/inward/record.url?scp=84924939925&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84924939925&partnerID=8YFLogxK
M3 - Article
AN - SCOPUS:84924939925
VL - 6
SP - 5310
EP - 5323
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 7
ER -