The role of S100A14 in epithelial ovarian tumors

被引:27
作者
Cho, Hanbyoul [1 ,3 ]
Shin, Ha-Yeon [1 ]
Kim, Sunghoon [2 ,3 ]
Kim, Jane Seon-Young [1 ]
Chung, Joon-Yong [4 ,5 ]
Chung, Eun Joo [6 ]
Chun, Kyung-Hee [7 ]
Hewitt, Stephen M. [4 ,5 ]
Kim, Jae-Hoon [1 ,3 ]
机构
[1] Yonsei Univ, Coll Med, Gangnam Severance Hosp, Dept Obstet & Gynecol, Seoul, South Korea
[2] Yonsei Univ, Coll Med, Severance Hosp, Dept Obstet & Gynecol, Seoul, South Korea
[3] Yonsei Univ, Coll Med, Inst Womens Life Med Sci, Seoul, South Korea
[4] NCI, Tissue Array Res Program, NIH, Bethesda, MD 20892 USA
[5] NCI, Appl Mol Pathol Lab, Pathol Lab, NIH, Bethesda, MD 20892 USA
[6] NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA
[7] Yonsei Univ, Coll Med, Dept Biochem & Mol Biol, Seoul, South Korea
基金
新加坡国家研究基金会;
关键词
Epithelial ovarian cancer; tumor marker; S100A14; shRNA; CANCER CELL-LINE; TRANSCRIPTIONAL REGULATION; EXPRESSION; INVASION; PROTEINS; FAMILY; DIFFERENTIATION; ADENOCARCINOMA; TUMORIGENESIS; PATHOGENESIS;
D O I
10.18632/oncotarget.1947
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
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.
引用
收藏
页码:3482 / 3496
页数:15
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