PATZ1 acts as a tumor suppressor in thyroid cancer via targeting p53-dependent genes involved in EMT and cell migration.
PATZ1 acts as a tumor suppressor in thyroid cancer via targeting p53-dependent genes involved in EMT and cell migration.
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DOI：
10.18632/oncotarget.2776
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发表时间：
2015-03-10
期刊：
影响因子：
--
通讯作者：
Fedele M
中科院分区：
文献类型：
--
作者：
Chiappetta G;Valentino T;Vitiello M;Pasquinelli R;Monaco M;Palma G;Sepe R;Luciano A;Pallante P;Palmieri D;Aiello C;Rea D;Losito SN;Arra C;Fusco A;Fedele M
PATZ 1是一种POZ-锌指蛋白，是一种重要的发育和癌症调控因子，但其作为癌基因或肿瘤抑制因子的功能仍存在争议。在这里，我们研究了它在甲状腺癌发生中的可能作用。我们证明PATZ 1在甲状腺癌中的表达较正常甲状腺组织下调，与细胞分化程度呈负相关。事实上，与乳头状组织型相比，PATZ 1在低分化和未分化甲状腺癌中的表达显著进一步下调，并且从分化到未分化甲状腺癌，其导致从细胞核到细胞质的越来越多的离域。三种甲状腺癌衍生细胞系的特征都是完全去分化的细胞，PATZ 1表达的恢复显著抑制了它们的恶性行为，包括体外增殖，锚定非依赖性生长，迁移和侵袭，以及体内肿瘤生长。与最近的研究表明PATZ 1在p53通路中的作用一致，我们发现甲状腺癌细胞中PATZ 1的异位表达激活了p53依赖性通路，对抗上皮-间质转化和细胞迁移，以防止侵袭。这些结果为PATZ 1在甲状腺癌进展中的潜在肿瘤抑制作用提供了见解，因此可能对甲状腺癌的预后和治疗具有潜在的临床意义。
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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影响因子：
4.4
作者：
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通讯作者：
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影响因子：
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7.3
作者：
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通讯作者：
Chieffi, P.
DOI：
10.1073/pnas.0909333107
发表时间：
2010-01-19
影响因子：
11.1
作者：
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通讯作者：
Lorens, James B.