Overexpression of nucleostemin contributes to an advanced malignant phenotype and a poor prognosis in oral squamous cell carcinoma.
Overexpression of nucleostemin contributes to an advanced malignant phenotype and a poor prognosis in oral squamous cell carcinoma.
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DOI：
10.1038/bjc.2014.539
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发表时间：
2014-12-09
影响因子：
8.8
通讯作者：
Ito, T.
中科院分区：
文献类型：
--
作者：
Yoshida, R.;Nakayama, H.;Nagata, M.;Hirosue, A.;Tanaka, T.;Kawahara, K.;Nakagawa, Y.;Matsuoka, Y.;Sakata, J.;Arita, H.;Hiraki, A.;Shinohara, M.;Ito, T.
核干细胞蛋白（NS）是维持干细胞特性所必需的，其在癌细胞中的功能仍然知之甚少。本研究旨在探讨NS对口腔鳞状细胞癌（OSCC）恶性程度的影响及其临床意义。我们使用NS过表达或敲低的OSCC细胞研究NS对OSCC增殖和侵袭的影响。我们评估了具有不同NS表达水平的细胞中STAT 3（信号转导子和转录激活子3）信号通路和下游靶点的激活。我们还对54例接受术前放化疗和手术治疗的口腔鳞癌患者进行了NS的免疫组化分析。NS的过表达显著增强了OSCC细胞的增殖和侵袭能力。另一方面，下调NS抑制了细胞的侵袭力。这些恶性表型的改变与STAT 3信号转导及其下游靶点的激活有关。免疫组化分析表明，高NS肿瘤表达水平显着相关的先进的T-阶段和N-阶段。此外，考克斯回归分析显示，NS状态（风险比，9.09; P=0.002）是口腔鳞癌患者的一个重要进展因素。我们的研究结果表明，针对NS可能提供一个有前途的治疗高度恶性口腔鳞癌。
Nucleostemin (NS) is essential for the maintenance of stem cell properties, the functions of which remain poorly understood in cancer cells. The purpose of this study was to explore the impact of NS on malignancy and its clinical significance in oral squamous cell carcinoma (OSCC) patients. We investigated the effects of NS on the proliferation and invasion of OSCC using NS-overexpressing or -knockdown OSCC cells. We assessed the activation of the STAT3 (signal transducer and activator of transcription 3) signalling pathway and the downstream targets in the cells with different expression levels of NS. An immunohistochemical analysis of NS was also performed in 54 OSCC patients who were treated with preoperative chemoradiotherapy and surgery. The overexpression of NS significantly enhanced the proliferation and invasive potential of OSCC cells. On the other hand, downregulation of NS suppressed the invasiveness of the cells. The alterations of these malignant phenotypes were associated with the activation of STAT3 signalling and its downstream targets. An immunohistochemical analysis demonstrated that a high NS tumour expression level significantly correlated with an advanced T-stage and N-stage. Furthermore, a Cox regression analysis revealed that the NS status (hazard ratio, 9.09; P=0.002) was a significant progression factor for OSCC patients. Our results suggest that targeting NS may provide a promising treatment for highly malignant OSCC.
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DOI：
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发表时间：
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影响因子：
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