title: EphA3 promotes malignant transformation of colorectal epithelial cells by upregulating oncogenic pathways.
abstract: Ephrin Type-A Receptor 3 (EphA3) belongs to the ephrin receptor subfamily of the protein tyrosine kinase family, and plays an important role in embryogenesis and neurogenesis. This study aimed to investigate the role of EphA3 in promoting malignant transformation of colorectal epithelial cells, and explore underlying molecular mechanisms. Colorectal cancer tissue specimens from 68 patients were analyzed for EphA3 expression. EphA3 expression levels were manipulated in rat colon epithelial cell lines. We found that EphA3 expression level in tumor tissues was associated with patient age (P = 0.015), tumor differentiation (P = 0.001), and lymph node metastasis (P = 0.039). Overexpression of EphA3 and its constitutively active mutants promoted colony formation, migration and invasion, and tumorigenicity of colon epithelial cells in nude mice. The cDNA and lncRNA microarray profiling data revealed that differentially expressed genes and lncRNAs in EphA3 or mutant-transfected cells were associated with cell proliferation, invasion and angiogenesis. Our findings reveal the mechanisms underlying the oncogenic activities of EphA3 in colorectal cells, which could provide novel targets for the prevention, early diagnosis, and treatment of colorectal cancer.
authors.affiliation: Department of Colorectal Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, China.
authors.forename: Mingqi
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Colorectal Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Colorectal Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Colorectal Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Department of Colorectal Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, China.
authors.forename: Fubin
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Colorectal Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, China.
authors.forename: Muhong
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Colorectal Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, China.
authors.forename: Dazhuang
authors.initials: D
authors.lastname: Miao
authors.affiliation: Department of Colorectal Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, China.
authors.forename: Xinyue
authors.initials: X
authors.lastname: Gu
authors.affiliation: Department of Colorectal Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, China.
authors.forename: Shixiong
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Department of Colorectal Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, China.
authors.forename: Binbin
authors.initials: B
authors.lastname: Cui
authors.affiliation: Department of Colorectal Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, China. Electronic address: tongjinxue_2008@163.com.
authors.forename: Jinxue
authors.initials: J
authors.lastname: Tong
authors.affiliation: Department of Colorectal Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, China. Electronic address: yuzw1974@hotmail.com.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Yu
mesh_terms: D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019295:Computational Biology; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009389:Neovascularization, Pathologic; D020411:Oligonucleotide Array Sequence Analysis; D009857:Oncogenes; D040901:Proteomics; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D036121:Receptor, EphA3; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
chemical_list: D062085:RNA, Long Noncoding; D012333:RNA, Messenger; C491718:EPHA3 protein, human; C110404:Epha3 protein, rat; D020794:Receptor Protein-Tyrosine Kinases; D036121:Receptor, EphA3
keywords: Colorectal epithelial cells; EphA3; Mutation; Transformation; Tumorigenicity