Overexpression of PBK/TOPK Contributes to Tumor Development and Poor Outcome of Esophageal Squamous Cell Carcinoma
Overexpression of PBK/TOPK Contributes to Tumor Development and Poor Outcome of Esophageal Squamous Cell Carcinoma
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DOI：
10.21873/anticanres.11244
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发表时间：
2016-12-01
影响因子：
2
通讯作者：
Otsuji, Eigo
中科院分区：
文献类型：
--
作者：
Ohashi, Takuma;Komatsu, Shuhei;Otsuji, Eigo
背景：pdz结合激酶/ t细胞源蛋白激酶（PBK/TOPK）是一种丝氨酸-苏氨酸激酶，在多种类型的癌症中过表达。PBK/TOPK通过抑制p53功能与肿瘤细胞的发展和进展相关。在这项研究中，我们通过在食管鳞状细胞癌（ESCC）中过表达PBK来检测其是否作为一种促癌因子。材料和方法：我们分析了PBK/TOPK在15个ESCC细胞系和54个1994年至2007年间治愈性切除的原发性ESCC肿瘤中的表达。结果：PBK/TOPK蛋白在93%（14/15）的ESCC细胞系和19%（10/54）的ESCC原发肿瘤样本中均有过表达，且与宏观外观和肿瘤深度显著相关。多因素分析显示，PBK/TOPK阳性与预后较差独立相关（p=0.0235，风险比=3.58）。使用特异性sirna敲低PBK/TOPK可抑制过表达PBK/TOPK的ESCC细胞系的细胞增殖、侵袭/迁移。结论：PBK/TOPK在ESCC中过表达，在肿瘤恶性潜能中起重要作用。
Background: PDZ-binding kinase/T-celloriginated protein kinase (PBK/TOPK) is a serine-threonine kinase and overexpressed in various types of cancer. PBK/TOPK is associated with tumor cell development and progression through suppression of p53 function. In this study, we tested whether PBK acts as a cancer-promoting factor by being overexpressed in esophageal squamous cell carcinoma (ESCC). Materials and Methods: We analyzed PBK/TOPK expression in 15 ESCC cell lines, and 54 primary ESCC tumors that were curatively resected between 1994 and 2007. Results: Overexpression of the PBK/TOPK protein was detected in 93% (14/15) ESCC cell lines and 19% (10/54) primary ESCC tumor samples, and significantly correlated with macroscopic appearance and tumor depth. PBK/TOPK positivity was independently associated with worse outcome in multivariate analysis (p=0.0235, hazard ratio=3.58). Knockdown of PBK/TOPK using specific siRNAs inhibited the cell proliferation, invasion/migration of PBK/TOPK-overexpressing ESCC cell lines. Conclusion: These findings suggest that PBK/TOPK plays a crucial role in tumor malignant potential through its overexpression in ESCC.