High KRT8 expression promotes tumor progression and metastasis of gastric cancer.
High KRT8 expression promotes tumor progression and metastasis of gastric cancer.
复制标题
KRT8高表达促进胃癌肿瘤进展和转移。
DOI：
10.1111/cas.13120
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发表时间：
2017-02
期刊：
影响因子：
5.7
通讯作者：
Shao S
中科院分区：
文献类型：
--
作者：
Fang J;Wang H;Liu Y;Ding F;Ni Y;Shao S
角蛋白8(keratin8，KRT8)是中间丝细胞骨架的主要成分，主要在单纯上皮组织中表达。KRT8的异常表达与多种肿瘤的进展和转移有关。然而，KRT8在胃癌(GC)中的作用尚不清楚。本研究对KRT8基因在人胃癌组织中的表达进行了研究，发现KRT8基因在人胃癌组织中的表达水平随着胃癌的进展和转移而上调。此外，KRT8过表达促进了人胃癌细胞的增殖和迁移，而siRNA下调KRT8只抑制了人胃癌细胞的迁移。整合素β1诱导的上皮-间充质转化仅存在于高KRT8细胞中。此外，KRT8过表达导致p-SMAD2/3水平和转化生长因子β依赖的信号转导事件增加。KRT8在胃癌中的表达与肿瘤的临床分期和预后有关。Kaplan-Meier分析证明KRT8与GC患者的总生存期相关，高表达KRT8的患者往往预后不良。此外，Cox比例风险分析显示，KRT8高表达是预后不良的标志。这些结果提供了KRT8的表达因此可能是一个生物标记物或潜在的治疗靶点，以确定患者的生存较差。
Keratin8 (KRT8) is the major component of the intermediate filament cytoskeleton and predominantly expressed in simple epithelial tissues. Aberrant expression of KRT8 is associated with multiple tumor progression and metastasis. However, the role of KRT8 in gastric cancer (GC) remains unclear. In this study, KRT8 expression was investigated and it was found to be upregulated along with human GC progression and metastasis at both mRNA and protein levels in human gastric cancer tissues. In addition, KRT8 overexpression enhanced the proliferation and migration of human gastric cancer cells, whereas the knock‐down of KRT8 by siRNA only inhibited migration of human gastric cancer cells. Integrinβ1‐FAK‐induced epithelial‐mesenchymal‐transition (EMT) only existed in the high KRT8 cells. Furthermore, KRT8 overexpression led to increase in p‐smad2/3 levels and TGFβ dependent signaling events. KRT8 expression in GC was related to tumor clinical stage and worse survival. Kaplan–Meier analysis proved that KRT8 was associated with overall survival of patients with GC that patients with high KRT8 expression tend to have unfavorable outcome. Moreover, Cox's proportional hazards analysis showed that high KRT8 expression was a prognostic marker of poor outcome. These results provided that KRT8 expression may therefore be a biomarker or potential therapeutic target to identify patients with worse survival.