EphB6 overexpression and Apc mutation together promote colorectal cancer
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Dan Xu2,*, Liang Yuan1,*, Xin Liu1, Mingqi Li1, Fubin Zhang1, XinYue Gu1, Dongwei Zhang4, Youlin Yang2, Binbin Cui1, Jinxue Tong1,*, Jin Zhou3,*, Zhiwei Yu1,*
1Department of Colorectal Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, China
2Digestive System Department, The First Affiliated Hospital of Harbin Medical University, Harbin, China
3Division of Hematology, The First Affiliated Hospital of Harbin Medical University, Harbin, China
4Department of Surgery, The Second Affiliated of Harbin Medical University, Harbin, China
*These authors contributed equally to this work
Zhiwei Yu, email: [email protected]
Jin Zhou, email: [email protected]
Keywords: EphB6, colorectal cancer, APC, biomarker, pathway analysis
Received: August 01, 2015 Accepted: April 10, 2016 Published: April 28, 2016
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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