Epstein-Barr virus latent antigens EBNA3C and EBNA1 modulate epithelial to mesenchymal transition of cancer cells associated with tumor metastasis.
Epstein-Barr virus latent antigens EBNA3C and EBNA1 modulate epithelial to mesenchymal transition of cancer cells associated with tumor metastasis.
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DOI：
10.1007/s13277-014-2941-6
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发表时间：
2015-04
期刊：
影响因子：
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通讯作者：
Kaul R
中科院分区：
文献类型：
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作者：
Gaur N;Gandhi J;Robertson ES;Verma SC;Kaul R
上皮-间质转化是肿瘤侵袭和转移的重要机制。我们以前曾报道，表达EB病毒（EBV）潜伏病毒抗原EBV核抗原EBNA 3C和/或EBNA 1的癌细胞显示出更高的运动性和迁移潜力，并在裸鼠模型中测试时具有增加转移的倾向。我们现在表明EBNA 3C和EBNA 1都可以调节癌细胞上皮向间质转化的关键细胞通路。我们的数据证实，EBNA 3C或EBNA 1的存在导致转录抑制子Slug和Snail的上调，间充质来源的波形蛋白的中间丝的上调，转录因子TCF 8/ZEB 1的上调，紧密连接蛋白ZO-1的下调和破坏，细胞粘附分子E-cadherin的下调，以及β-catenin的核转位。我们进一步表明，原发性肿瘤以及转移性病变来源于EBV抗原表达癌细胞在裸鼠模型显示EMT标志物表达模式，表明他们更大的倾向间质转化。
Epithelial–mesenchymal transition is an important mechanism in cancer invasiveness and metastasis. We had previously reported that cancer cells expressing Epstein–Barr virus (EBV) latent viral antigens EBV nuclear antigen EBNA3C and/ or EBNA1 showed higher motility and migration potential and had a propensity for increased metastases when tested in nude mice model. We now show that both EBNA3C and EBNA1 can modulate cellular pathways critical for epithelial to mesenchymal transition of cancer cells. Our data confirms that presence of EBNA3C or EBNA1 result in upregulation of transcriptional repressor Slug and Snail, up-regulation of intermediate filament of mesenchymal origin vimentin, upregulation of transcription factor TCF8/ZEB1, downregulation as well as disruption of tight junction zona occludens protein ZO-1, downregulation of cell adhesion molecule E-cadherin, and nuclear translocation of β-catenin. We further show that the primary tumors as well as metastasized lesions derived from EBV antigen-expressing cancer cells in nude mice model display EMT markers expression pattern suggesting their greater propensity to mesenchymal transition.