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S100A14在上皮性卵巢肿瘤中的作用。

The role of S100A14 in epithelial ovarian tumors.

作者信息

Cho Hanbyoul, Shin Ha-Yeon, Kim Sunghoon, Kim Jane Seon-Young, Chung Joon-Yong, Chung Eun Joo, Chun Kyung-Hee, Hewitt Stephen M, Kim Jae-Hoon

机构信息

Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.

出版信息

Oncotarget. 2014 Jun 15;5(11):3482-96. doi: 10.18632/oncotarget.1947.

Abstract

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.

摘要

S100A14是一种EF手型钙结合蛋白,据报道它参与多种恶性肿瘤的进展。然而,其在卵巢癌中的作用尚未阐明。在本研究中,我们调查了S100A14在上皮性卵巢癌(EOC)中的表达意义及其作用机制。在RNA和蛋白质水平上,S100A14在转化细胞中均过表达。免疫组织化学染色显示,S100A14表达与晚期(P<0.001)和肿瘤低分级(P<0.001)相关。此外,S100A14过表达是总生存的独立预后因素(HR = 4.53,P = 0.029)。我们还通过在EOC细胞中采用慢病毒介导的过表达和敲低来研究S100A14的功能作用。S100A14过表达促进细胞增殖、肿瘤发生、迁移和侵袭,而S100A14敲低则抑制这些特性。过表达S100A14的TOV112D细胞在异种移植小鼠中也表现出更大的肿瘤生长潜力。S100A14通过PI3K/Akt途径促进EOC细胞中的这种恶性表型。综上所述,我们的数据表明S100A14在EOC进展中起关键作用,其过表达与不良预后相关。对S100A14分子机制的进一步研究可能会导致开发出一种新的卵巢癌治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2024/4116497/58f9de8151d4/oncotarget-05-3482-g001.jpg

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