Human cytomegalovirus infection enhances cell proliferation, migration and upregulation of EMT markers in colorectal cancer-derived stem cell-like cells.
Human cytomegalovirus infection enhances cell proliferation, migration and upregulation of EMT markers in colorectal cancer-derived stem cell-like cells.
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DOI：
10.3892/ijo.2017.4135
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发表时间：
2017-11
影响因子：
5.2
通讯作者：
Chan YJ
中科院分区：
文献类型：
--
作者：
Teo WH;Chen HP;Huang JC;Chan YJ
越来越多的证据表明持续性人巨细胞病毒（HCMV）感染与癌症之间存在联系。虽然HCMV在癌症中的作用仍然难以捉摸，但最近的研究揭示了HCMV核酸和蛋白质在不同癌症类型中的存在，如胶质母细胞瘤，结直肠癌，乳腺癌，前列腺癌和神经母细胞瘤。虽然HCMV可能与肿瘤转化没有直接关系，但肿瘤组织中HCMV DNA的存在与癌症患者临床结局的改变有关。然而，结直肠癌（CRC）和HCMV之间的关联机制尚不清楚。在这项研究中，我们研究了HCMV感染对CRC或其衍生细胞的影响。增殖和迁移测定显示CRC衍生的HT29和SW480“干细胞样”细胞中的高感染效率。在HCMV感染24、48和72小时后，HT 29和SW 480亲本细胞和干细胞样细胞均显示出细胞增殖和活力的显著增加（p<0.0001）。此外，HCMV感染促进细胞迁移。这些结果证明了在HCMV感染后CRC细胞系中的显著表型改变。使用上皮间质转化（EMT）试验，我们证明了EMT标志物和驱动基因在病毒感染过程中上调。与感染后第7天的未感染细胞相比，与CRC细胞的增殖和迁移相关的WNT信号通路在HCMV感染的细胞中上调（6倍）。
Increasing evidence suggests a link between persistent human cytomegalovirus (HCMV) infection and cancer. Although the role of HCMV in cancer is still elusive, recent studies revealed the presence of HCMV nucleic acids and proteins in different cancer types such as glioblastoma, colorectal, breast, and prostate cancers, and neuroblastoma. Although HCMV may not be directly associated with the neoplastic transformation, the presence of HCMV DNA in the tumorous tissue has been associated with altered clinical outcomes in cancer patients. However, the mechanisms involved in the association between colorectal cancer (CRC) and HCMV are unclear. In this study, we investigated the influence of HCMV infection on CRC or their derived cells. Proliferation and migration assays revealed a high infection efficiency in CRC-derived HT29 and SW480 'stem-like' cells. After 24, 48 and 72 h of HCMV infection, both HT29 and SW480 parental and stem-like cells showed a significant increase in cell proliferation and viability (p<0.0001). Moreover, HCMV infection promoted cell migration. These results demonstrate a significant phenotypic alteration in the CRC cell line upon HCMV infection. Using epithelial to mesenchymal transition (EMT) assays, we demonstrated that the EMT markers and driver genes were upregulated during the virus infection. The WNT signaling pathway, which is associated with the proliferation and migration of CRC cells, was upregulated (6-fold) in HCMV-infected cells as compared to the non-infected cells at day 7 from infection.
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作者：
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通讯作者：
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通讯作者：
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