EphB6 overexpression and Apc mutation together promote colorectal cancer.
EphB6 overexpression and Apc mutation together promote colorectal cancer.
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EphB6过表达和Apc突变共同促进结直肠癌
DOI：
10.18632/oncotarget.9080
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发表时间：
2016-05-24
期刊：
影响因子：
--
通讯作者：
Yu Z
中科院分区：
文献类型：
--
作者：
Xu D;Yuan L;Liu X;Li M;Zhang F;Gu XY;Zhang D;Yang Y;Cui B;Tong J;Zhou J;Yu Z
产生红细胞生成素的肝细胞（Eph）家族酪氨酸激酶在肿瘤发生和癌症侵袭中起重要作用。在这项研究中，我们研究了EphB6在体外和体内结直肠上皮细胞致癌转化中的作用。与正常组织相比，EphB6在人结直肠癌（CRC）组织中上调，并且其过表达促进IMCE结直肠腺瘤细胞的增殖、迁移和侵袭，其中一个Apc等位基因突变。EphB6过表达与Apc突变一起导致体内结直肠肿瘤的发展。使用从EphB6过表达的IMCE和对照细胞分离的mRNA和lncRNA的表达微阵列揭示了大量参与癌症相关功能和途径的失调基因。本研究首次证明EphB6过表达与Apc基因突变一起可增强结直肠上皮细胞的增殖、侵袭和转移。差异表达基因的微阵列数据和途径分析提供了对EphB6促进肿瘤发生和癌症进展的可能调节机制的深入了解。EphB6过表达可能代表一种新的、有效的生物标志物，可预测CRC肿瘤中的细胞增殖、侵袭和转移模式。
The erythropoietin-producing hepatocyte (Eph) family tyrosine kinases play important roles in tumorigenesis and cancer aggression. In this study, we investigated the role of EphB6 in oncogenic transformation of colorectal epithelial cells in vitro and in vivo. EphB6 is upregulated in human colorectal cancer (CRC) tissues as compared to normal tissues, and its overexpression promotes proliferation, migration and invasion by IMCE colorectal adenoma cells, in which one Apc allele is mutated. EphB6 overexpression together with Apc mutation leads to the development of colorectal tumors in vivo. Expression microarrays using mRNAs and lncRNAs isolated from EphB6-overexpresssing IMCE and control cells revealed a large number of dysregulated genes involved in cancer-related functions and pathways. The present study is the first to demonstrate that EphB6 overexpression together with Apc gene mutations may enhance proliferation, invasion and metastasis by colorectal epithelial cells. Microarray data and pathway analysis of differentially expressed genes provided insight into possible EphB6-regulated mechanisms promoting tumorigenesis and cancer progression. EphB6 overexpression may represent a novel, effective biomarker predictive of cell proliferation, invasion and metastasis patterns in CRC tumors.
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