Ephrin Type-A Receptor 3 (EphA3) and Ephrin Type-B Receptor 6 (EphB6) belong to the ephrin receptor group consisting of the largest subset of receptor tyrosine kinases (RTKs) and are essential for neurogenesis and embryogenesis. The current study aimed to evaluate their functional roles in transforming colorectal epithelial cells and dissect the underlying molecular mechanisms. We observed altered EphA3 and EphB6 expression in tumor tissues as compared to normal tissues in a tissue microarray study. Enforced EphB6 expression promoted IMCE cell proliferation, migration, and invasion in vitro and tumor formation in nude mice, with a stronger oncogenic activity than EphA3. Pathway analysis of differentially expressed genes from a gene microarray study provided important insight into potential mechanisms through which EphB6 may regulate the malignant transformation of colorectal epithelial cells. This study represents the first demonstration of EphB6 in enhancing colorectal epithelial cell transformation, suggesting its stipulative role in the early-stage of colorectal tumorigenesis. Our findings primarily uncover novel biomarkers and therapeutic targets of colorectal cancer.

中文翻译：

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确定 Ephrin B 型受体 6 和 A 型受体 3 对促进结直肠上皮细胞恶性转化的影响。

Ephrin Type-A Receptor 3 (EphA3) 和 Ephrin Type-B Receptor 6 (EphB6) 属于 ephrin 受体组，由最大的受体酪氨酸激酶 (RTK) 子集组成，对神经发生和胚胎发生至关重要。目前的研究旨在评估它们在转化结直肠上皮细胞中的功能作用并剖析潜在的分子机制。在组织微阵列研究中，我们观察到与正常组织相比，肿瘤组织中 EphA3 和 EphB6 的表达发生了改变。强制的 EphB6 表达促进 IMCE 细胞体外增殖、迁移和侵袭以及裸鼠肿瘤形成，具有比 EphA3 更强的致癌活性。来自基因微阵列研究的差异表达基因的通路分析提供了对 EphB6 可能调节结直肠上皮细胞恶性转化的潜在机制的重要见解。这项研究首次证明了 EphB6 在增强结直肠上皮细胞转化方面的作用，表明其在结直肠肿瘤发生的早期阶段具有规定的作用。我们的研究结果主要揭示了结直肠癌的新型生物标志物和治疗靶点。