Human papillomavirus type 16 oncoprotein E7 suppresses cadherin-mediated cell adhesion via ERK and AP-1 signaling.
Human papillomavirus type 16 oncoprotein E7 suppresses cadherin-mediated cell adhesion via ERK and AP-1 signaling.
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DOI：
10.3892/ijo_00000341
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发表时间：
2009-08
影响因子：
5.2
通讯作者：
Hong Yuan;S. Ito;T. Senga;T. Hyodo;T. Kiyono;F. Kikkawa;M. Hamaguchi
中科院分区：
文献类型：
--
作者：
Hong Yuan;S. Ito;T. Senga;T. Hyodo;T. Kiyono;F. Kikkawa;M. Hamaguchi
人乳头瘤病毒(HPV)是宫颈癌的主要致病因素。HPV-16是在HPV相关癌症中发现的最常见的高危HPV基因。我们研究了HPV-16E7癌蛋白对钙粘附素介导的细胞黏附的影响。E7基因的表达可显著抑制3Y1细胞中钙粘附素介导的细胞黏附。这种抑制与N-钙粘附素在转录水平的表达减少有关。用MEK抑制剂处理表达E7(E7-3Y1)的3Y1细胞后，细胞粘附素介导的细胞黏附和N-钙粘蛋白在细胞-细胞接触部位的积聚得到恢复。此外，抑制AP-1转录因子元件c-jun可恢复E7-3Y1细胞N-钙粘蛋白的表达和钙粘附素介导的细胞黏附。综上所述，我们的结果表明，E7通过MEK-ERK和AP-1信号通路调节钙粘附素的表达，从而调节钙粘附素介导的细胞黏附。
Human papillomaviruses (HPV) are the main etiological factor for cervical carcinoma. HPV-16 is the most prevalent high-risk HPV-genotype found in HPV-associated cancers. We studied the effect of HPV-16 E7 oncoprotein on cadherin-mediated cell adhesion. The expression of E7 strongly suppressed the cadherin-mediated cell adhesion in the rat fibroblast cell line 3Y1. This suppression was associated with the decreased expression of N-cadherin at the transcriptional level. The treatment of 3Y1 cells that express E7 (E7-3Y1) with MEK inhibitor recovered the cadherin-mediated cell adhesion together with the accumulation of N-cadherin at the cell-cell contact site. Moreover, the suppression of c-Jun, which is the element of AP-1 transcriptional factor, leads to the recovery of N-cadherin expression and cadherin-mediated cell adhesion in E7-3Y1 cells. Taken together, our results demonstrate that E7 regulates cadherin-mediated cell adhesion through the modulation of cadherin expression via the MEK-ERK and AP-1 signaling pathway.