Overexpression of YWHAZ relates to tumor cell proliferation and malignant outcome of gastric carcinoma.
Overexpression of YWHAZ relates to tumor cell proliferation and malignant outcome of gastric carcinoma.
复制标题
DOI：
10.1038/bjc.2013.65
复制
发表时间：
2013-04-02
影响因子：
8.8
通讯作者：
Otsuji, E.
中科院分区：
文献类型：
--
作者：
Nishimura, Y.;Komatsu, S.;Ichikawa, D.;Nagata, H.;Hirajima, S.;Takeshita, H.;Kawaguchi, T.;Arita, T.;Konishi, H.;Kashimoto, K.;Shiozaki, A.;Fujiwara, H.;Okamoto, K.;Tsuda, H.;Otsuji, E.
一些研究表明，YWHAZ(14-3-3ζ)属于14-3-3蛋白家族，与癌症的发生和发展有关。我们检测了YWHAZ是否通过其在胃癌中的激活/过表达而发挥促癌基因的作用。我们分析了2001-2003年间在本院进行根治性切除的7个GC细胞系和141个原发肿瘤。YWHAZ蛋白在胃癌细胞系(6/7株，85.7%)和原发肿瘤标本(72/141例，51%)中高表达，且与较大的肿瘤大小、静脉和淋巴侵犯、较深的肿瘤深度、较高的病理分期和复发率显著相关。YWHAZ过表达肿瘤的患者在强度和比例表达依赖的方式上都比那些不表达的肿瘤患者的总存活率更低。在多因素分析中，YWHAZ阳性与较差的预后独立相关(P=0.0491，危险比2.3(1.003-5.304))。用几种特定的siRNAs抑制YWHAZ的表达可抑制YWHAZ过表达的GC细胞的增殖、迁移和侵袭。YWHAZ蛋白的高表达与miR-375在原发癌组织中的低表达显著相关(P=0.0047)。这些发现表明，YWHAZ通过其过度表达在肿瘤细胞的增殖中起着关键作用，并突出了其作为胃癌预后因子和潜在治疗靶点的作用。
Several studies have demonstrated that YWHAZ (14-3-3ζ), included in the 14-3-3 family of proteins, has been implicated in the initiation and progression of cancers. We tested whether YWHAZ acted as a cancer-promoting gene through its activation/overexpression in gastric cancer (GC). We analysed 7 GC cell lines and 141 primary tumours, which were curatively resected in our hospital between 2001 and 2003. Overexpression of the YWHAZ protein was frequently detected in GC cell lines (six out of seven lines, 85.7%) and primary tumour samples of GC (72 out of 141 cases, 51%), and significantly correlated with larger tumour size, venous and lymphatic invasion, deeper tumour depth, and higher pathological stage and recurrence rate. Patients with YWHAZ-overexpressing tumours had worse overall survival rates than those with non-expressing tumours in both intensity and proportion expression-dependent manner. YWHAZ positivity was independently associated with a worse outcome in multivariate analysis (P=0.0491, hazard ratio 2.3 (1.003–5.304)). Knockdown of YWHAZ expression using several specific siRNAs inhibited the proliferation, migration, and invasion of YWHAZ-overexpressing GC cells. Higher expression of the YWHAZ protein was significantly associated with the lower expression of miR-375 in primary GC tissues (P=0.0047). These findings suggest that YWHAZ has a pivotal role in tumour cell proliferation through its overexpression, and highlight its usefulness as a prognostic factor and potential therapeutic target in GC.
登录
查看更多内容
影响因子：
7.3
作者：
MAESAWA, C;TAMURA, G;SATODATE, R
通讯作者：
SATODATE, R
影响因子：
3.7
作者：
Garnis, C;Coe, BP;Lam, WL
通讯作者：
Lam, WL
影响因子：
4.3
作者：
Fang, DC;Wang, RQ;Luo, YH
通讯作者：
Luo, YH
影响因子：
11.2
作者：
Neal CL;Yao J;Yang W;Zhou X;Nguyen NT;Lu J;Danes CG;Guo H;Lan KH;Ensor J;Hittelman W;Hung MC;Yu D
通讯作者：
Yu D
影响因子：
82.9
作者：
Li, Yang;Zou, Lihua;Li, Qiyuan;Haibe-Kains, Benjamin;Tian, Ruiyang;Li, Yan;Desmedt, Christine;Sotiriou, Christos;Szallasi, Zoltan;Iglehart, J. Dirk;Richardson, Andrea L.;Wang, Zhigang Charles
通讯作者：
Wang, Zhigang Charles