MUC1 induced by Epstein-Barr virus latent membrane protein 1 causes dissociation of the cell-matrix interaction and cellular invasiveness via STAT signaling
MUC1 induced by Epstein-Barr virus latent membrane protein 1 causes dissociation of the cell-matrix interaction and cellular invasiveness via STAT signaling
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DOI：
10.1128/jvi.02222-06
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发表时间：
2007-02-01
影响因子：
5.4
通讯作者：
Pagano, Joseph S.
中科院分区：
文献类型：
--
作者：
Kondo, Satoru;Yoshizaki, Tornokazu;Pagano, Joseph S.
细胞粘附的破坏是导致肿瘤扩散的重要病理生物学步骤。粘蛋白I（MUC 1）是一种粘液糖蛋白，表达于许多组织及其癌的上皮细胞表面。MUC1在肿瘤的侵袭和转移中起着重要作用，尤其是在对抗细胞粘附方面。我们已经表明，病毒感染，特别是由人类肿瘤病毒EB病毒（EBV）诱导的细胞侵袭和转移因子的频谱。在这里，我们表明，MUC1的表达增加，在不同的潜伏性EB病毒感染的细胞系，表达潜伏膜蛋白1（LMP1），主要的病毒癌蛋白，和MUC1的水平被抑制的显性负突变体LMP1的表达。LMP1在EBV阴性鼻咽细胞系中的表达通过结合STAT1和STAT3激活MUC1启动子诱导MUC1表达。最后，LMP 1降低细胞粘附能力，其通过用MUC1小干扰RNA（siRNA）抑制MUC1表达而恢复。此外，LMP1增加细胞侵袭力，这被MUC1 siRNA抑制。因此，LMP 1诱导MUC 1，MUC 1是在肿瘤细胞的脱离和释放的早期步骤中重要的因子，其沿着其他侵袭性和血管生成因子的诱导，可以联合收割机在复杂的连续过程中起作用，最终导致EBV感染的肿瘤细胞的转移。
Disruption of cellular adhesion is an essential pathobiologic step leading to tumor dissemination. Mucin I (MUC1) is a mucinous glycoprotein expressed at the surfaces of epithelial cells in many tissues and their carcinomas. MUC1 plays crucial roles in tumor invasion and metastasis, especially in opposing cell adhesion. We have shown that virus infection, specifically by the human tumor virus Epstein-Barr virus (EBV) induces a spectrum of cellular invasiveness and metastasis factors. Here we show that expression of MUC1 is increased in diverse latently EBV-infected cell lines that express latent membrane protein 1 (LMP1), the main viral oncoprotein, and that the level of MUC1 was suppressed by expression of a dominant-negative mutant of LMP1. Expression of LMP1 in EBV-negative nasopharyngeal cell lines induces expression of MUC1 through activation of the MUC1 promoter via binding of STAT1 and STAT3. Finally, LMP1 reduces cell adhesion ability, which is restored by inhibition of MUC1 expression with MUC1 small interfering RNA (siRNA). In addition, LMP1 increases cell invasiveness, which is suppressed by MUC1 siRNA. Thus, LMP1 induces MUC1, a factor important in an early step of detachment and release of tumor cells, which along with induction of other invasiveness and angiogenic factors may combine to act in a complex sequential process that culminates in metastasis of EBV-infected tumor cells.