Reduced MAGI3 level by HPV18E6 contributes to Wnt/β-catenin signaling activation and cervical cancer progression,FEBS Open Bio

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Reduced MAGI3 level by HPV18E6 contributes to Wnt/β-catenin signaling activation and cervical cancer progression
FEBS Open Bio ( IF 2.8 ) Pub Date : 2021-09-12 , DOI: 10.1002/2211-5463.13298
Zhuoli Yang ₁ , Hua Liu ₁ , Ran Song ₁ , Wenxiu Lu ₁ , Haibo Wang ₁ , Siyu Gu ₁ , Xuedi Cao ₁ , Yibin Chen ₁ , Jihuan Liang ₁ , Qiong Qin ₁ , Xiaomei Yang ₁ , Duiping Feng ₂ , Junqi He ₁

Affiliation

Human papillomavirus type 18 (HPV18) has high carcinogenic power in invasive cervical cancer (ICC) development. However, the underlying mechanism remains elusive. The carcinogenic properties of HPV18 require the PDZ-binding motif of its E6 oncoprotein (HPV18 E6) to degrade its target PSD95/Dlg/ZO-1 (PDZ) proteins. In this study, we demonstrated that the PDZ protein membrane-associated guanylate kinase, WW and PDZ domain containing 3 (MAGI3) inhibited the Wnt/β-catenin pathway, and subsequently cervical cancer (CC) cell migration and invasion, via decreasing β-catenin levels. By reducing MAGI3 protein levels, HPV18 E6 promoted CC cell migration and invasion through activation of Wnt/β-catenin signaling. Furthermore, HPV18 rather than HPV16 was preferentially associated with the downregulation of MAGI3 and activation of the Wnt/β-catenin pathway in CC. These findings shed light on the mechanism that gives HPV18 its high carcinogenic potential in CC progression.

中文翻译：

HPV18E6 降低 MAGI3 水平有助于 Wnt/β-连环蛋白信号激活和宫颈癌进展

人乳头瘤病毒 18 型 (HPV18) 在浸润性宫颈癌 (ICC) 的发展中具有很高的致癌性。然而，潜在的机制仍然难以捉摸。HPV18 的致癌特性需要其 E6 癌蛋白 (HPV18 E6) 的 PDZ 结合基序来降解其靶 PSD95/Dlg/ZO-1 (PDZ) 蛋白。在这项研究中，我们证明了 PDZ 蛋白膜相关鸟苷酸激酶、WW 和 PDZ 结构域含有 3 (MAGI3) 通过降低 β-抑制 Wnt/β-catenin 通路，随后抑制宫颈癌 (CC) 细胞迁移和侵袭。连环蛋白水平。通过降低 MAGI3 蛋白水平，HPV18 E6 通过激活 Wnt/β-catenin 信号促进 CC 细胞迁移和侵袭。此外，HPV18 而非 HPV16 优先与 MAGI3 的下调和 CC 中 Wnt/β-catenin 通路的激活相关。这些发现揭示了 HPV18 在 CC 进展中具有高致癌潜力的机制。

更新日期：2021-11-03

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