The role of S100A14 in epithelial ovarian tumors.
The role of S100A14 in epithelial ovarian tumors.
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DOI：
10.18632/oncotarget.1947
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发表时间：
2014-06-15
期刊：
影响因子：
--
通讯作者：
Kim JH
中科院分区：
文献类型：
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作者：
Cho H;Shin HY;Kim S;Kim JS;Chung JY;Chung EJ;Chun KH;Hewitt SM;Kim JH
S100 A14是一种EF-手型钙结合蛋白，据报道与许多恶性肿瘤的进展有关。然而，它在卵巢癌中的作用尚未明确。本研究旨在探讨S100 A14在卵巢上皮性癌中的表达及其作用机制。在RNA和蛋白质水平上，S100 A14在转化细胞中过表达。免疫组化结果显示S100 A14蛋白表达与肿瘤的临床分期及分级有关（P <0.001）。S100 A14过表达是影响总生存率的独立预后因素（HR = 4.53，P = 0.029）。我们还研究了S100 A14的功能作用，采用慢病毒介导的过表达和敲低EOC细胞。S100 A14过表达促进细胞增殖、肿瘤发生、迁移和侵袭，而S100 A14敲低抑制这些特性。过表达S100 A14的TOV 112 D细胞在异种移植小鼠中也表现出更大的肿瘤生长潜力。S100 A14通过PI 3 K/Akt通路促进EOC细胞中的这种恶性表型。综上所述，我们的数据表明S100 A14在EOC进展中具有关键作用，并且其过表达与不良预后相关。对S100 A14分子机制的进一步研究可能会导致卵巢癌新的治疗靶点的开发。
S100A14 is an EF-hand calcium-binding protein that has been reported to be involved in the progression of many malignancies. However, its role in ovarian cancer has not yet been clarified. In this study, we investigated the significance of S100A14 expression in epithelial ovarian cancers (EOCs) as well as it's mechanism of action. On both RNA and protein levels, S100A14 was overexpressed in transformed cells. Immunohistochemical staining demonstrated that S100A14 expression was associated with advanced stage (P < 0.001) and poor tumor grade (P < 0.001). Moreover, S100A14 overexpression was an independent prognostic factor for overall survival (HR = 4.53, P = 0.029). We also investigated S100A14's functional role by employing lentiviral-mediated overexpression and knockdown in EOC cells. S100A14 overexpression promoted cell proliferation, tumorigenesis, migration, and invasion, whereas S100A14 knockdown inhibited these properties. TOV112D cells that overexpressed S100A14 also exhibited greater tumor growth potential in xenografted mice. S100A14 promoted such a malignant phenotype in EOC cells through the PI3K/Akt pathway. Taken together, our data indicate that S100A14 has a crucial role in EOC progression, and its overexpression is associated with poor prognosis. Further study of S100A14's molecular mechanisms may lead to the development of a novel therapeutic target for ovarian cancer.