Decreased TOB1 expression and increased phosphorylation of nuclear TOB1 promotes gastric cancer.
Decreased TOB1 expression and increased phosphorylation of nuclear TOB1 promotes gastric cancer.
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TOB1表达减少和核TOB1磷酸化增加促进胃癌发生
DOI：
10.18632/oncotarget.20749
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发表时间：
2017-09-26
期刊：
影响因子：
--
通讯作者：
Yu J
中科院分区：
文献类型：
--
作者：
Guan R;Peng L;Wang D;He H;Wang D;Zhang R;Wang H;Hao H;Zhang J;Song H;Sui S;Meng X;Cui X;Bai J;Sun W;Fu S;Yu J
TOB1是BTG/TOB蛋白家族的一员，具有抑制肿瘤细胞增殖的作用。我们之前观察到胃癌（GC）中TOB1的下调和磷酸化。在这里，我们研究了to1在胃癌中的亚细胞分布和临床意义。对341例胃癌及相应的正常胃组织进行免疫组化分析，胃癌组织中核TOB1表达低于正常组织（80.4% vs. 92.4%），核TOB1表达降低与TNM分期高相关。相比之下，胃癌组织中核TOB1的磷酸化水平高于正常胃组织（66.0%比36.4%），并与低分化和高TNM期肿瘤相关。肠型胃癌和核TOB1磷酸化增加的患者总生存期较差。多因素生存分析显示，磷酸化的TOB1核浓度是肠型胃癌的独立预后因素。与表达带有核定位信号的TOB1细胞相比，含有其核输出信号突变的TOB1过表达可抑制GC细胞的增殖、迁移和侵袭。因此，在肠型胃癌中，TOB1表达的减少和核TOB1磷酸化的增加与肿瘤的侵袭性行为和不良预后有关。此外，TOB1核保留对其抗扩散活性至关重要。
TOB1, a member of the BTG/TOB protein family, inhibits tumor cell proliferation. We previously observed down-regulation and phosphorylation of TOB1 in gastric cancer (GC). Here, we examined the subcellular distribution and clinical significance of TOB1 expression and phosphorylation in GC. Immunohistochemical analysis of 341 primary GC and corresponding normal gastric tissue samples demonstrated that nuclear TOB1 expression was lower in GC than normal tissue (80.4% vs. 92.4%), and decreased nuclear TOB1 expression correlated with high TNM stage. By contrast, phosphorylation of nuclear TOB1 was higher in GC than normal gastric tissue (66.0% vs. 36.4%), and was associated with poorly differentiated and high TNM stage tumors. Patients with intestinal type GC and increased nuclear TOB1 phosphorylation had poor overall survival. Multivariate survival analysis indicated the nuclear concentration of phosphorylated TOB1 was an independent prognostic factor for intestinal type GC. Overexpression of TOB1 containing mutations in its nuclear export signal inhibited GC cell proliferation, migration, and invasion compared to cells expressing TOB1 with the nuclear localization signal. Thus, decreased TOB1 expression and increased phosphorylation of nuclear TOB1 is associated with aggressive tumor behavior and poor prognosis in intestinal type GC. Additionally, TOB1 nuclear retention is critical for its anti-proliferative activity.
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影响因子：
29.4
作者：
Tan IB;Ivanova T;Lim KH;Ong CW;Deng N;Lee J;Tan SH;Wu J;Lee MH;Ooi CH;Rha SY;Wong WK;Boussioutas A;Yeoh KG;So J;Yong WP;Tsuburaya A;Grabsch H;Toh HC;Rozen S;Cheong JH;Noh SH;Wan WK;Ajani JA;Lee JS;Tellez MS;Tan P
通讯作者：
Tan P
ErbB-2.1 (T0B1) 转导子对人肺癌细胞增殖和转移的体外抑制作用
影响因子：
8.2
作者：
Jiao, Yang;Sun, Ke-kang;Fan, Sai-jun
通讯作者：
Fan, Sai-jun
影响因子：
9.7
作者：
Ito, Y;Suzuki, T;Miyauchi, A
通讯作者：
Miyauchi, A
影响因子：
9.7
作者：
Iwanaga, K;Sueoka, N;Sueoka, E
通讯作者：
Sueoka, E
影响因子：
3.8
作者：
Yu, Jingcui;Liu, Peng;Cui, Xiaobo;Sui, Yu;Ji, Guohua;Guan, Rongwei;Sun, Donglin;Ji, Wei;Liu, Fangli;Liu, An;Zhao, Yuzhen;Yu, Yang;Jin, Yan;Bai, Jing;Geng, Jingshu;Xue, Yingwei;Qi, Jiping;Lee, Ki-Young;Fu, Songbin
通讯作者：
Fu, Songbin