Original ArticleEphA3 promotes malignant transformation of colorectal epithelial cells by upregulating oncogenic pathways

- Altered EphA3 expression or activity is associated with carcinogenesis, including colorectal cancer.
- Our study showed that EphA3 overexpression in tumor tissues was associated with patient age, tumor differentiation, and lymph node metastasis. The expression of EphA3 and its constitutively active mutants promoted colony formation, migration, and invasion, and induced tumorigenicity of colon epithelial cells in nude mice.
- In addition, cDNA and lncRNA microarray profiling data revealed that differentially expressed genes and lncRNAs in EphA3-expressing cells were associated with cell proliferation, invasion, and angiogenesis.
- The findings of our study reveal additional mechanisms underlying the oncogenic effects of EphA3 on colorectal cells, which could provide novel targets for the prevention, early diagnosis, and treatment of colorectal cancer.

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.