EphA3 promotes malignant transformation of colorectal epithelial cells by upregulating oncogenic pathways.
EphA3 promotes malignant transformation of colorectal epithelial cells by upregulating oncogenic pathways.
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EphA3 通过上调致癌途径促进结直肠上皮细胞的恶性转化。
DOI：
10.1016/j.canlet.2016.10.004
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发表时间：
2016-12
期刊：
影响因子：
--
通讯作者：
Zhiwei Yu
中科院分区：
文献类型：
--
作者：
Liang Yuan Fubin Zhang Muhong Wang;Dazhuang Miao Xinyue Gu Shixiong Jiang;Binbin Cui Jinxue Tong;Zhiwei Yu
Ephrin A型受体3（EphA3）属于蛋白酪氨酸激酶家族中的Ephrin受体亚家族，在胚胎发育和神经发生中起重要作用。本研究旨在探讨EphA3在大肠上皮细胞恶性转化中的作用，并探讨其分子机制。分析来自68名患者的结直肠癌组织标本的EphA3表达。在大鼠结肠上皮细胞系中操纵EphA3表达水平。我们发现EphA3在肿瘤组织中的表达水平与患者年龄（P = 0.015）、肿瘤分化程度（P = 0.001）和淋巴结转移（P = 0.039）相关。EphA3及其组成型活性突变体的过表达促进了结肠上皮细胞在裸鼠体内的集落形成、迁移和侵袭以及致瘤性。cDNA和lncRNA微阵列分析数据显示，EphA3或mu转染细胞中差异表达的基因和lncRNA与细胞增殖、侵袭和血管生成相关。我们的研究结果揭示了EphA3在结直肠细胞中致癌活性的机制，这可能为结直肠癌的预防，早期诊断和治疗提供新的靶点。
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.
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影响因子：
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