Abstract
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.
Highlights
Colorectal cancer (CRC) is a heterogeneous disease, resulting from complex interactions between genetic and environmental factors
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
adenomatous polyposi coli (APC) was progressively downregulated and EphB6 was upregulated as disease progressed toward adenocarcinoma, but both were highly expressed in adenomas (Figure 1A and 1B, Tables 1 and 2)
Summary
Colorectal cancer (CRC) is a heterogeneous disease, resulting from complex interactions between genetic and environmental factors. CRC is the third most common cancer and the fourth leading cause of cancer-related deaths worldwide [2]. In China, CRC ranks the fifth among cancer deaths, with a continually increasing incidence [3]. Despite surgical removal of the primary tumor, a significant proportion of CRC patients experience recurrence and may die within 5 years postsurgery [4]. Earlier diagnosis and discovery of recurrence after surgery are critical for effective treatment of CRC. Mechanisms underlying CRC development are currently unclear. Identification of novel diagnostic biomarkers sensitive and specific to CRC is urgently needed and would promote development of more effective therapeutics
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