Centre de Recherche sur le Cancer de l'Université Laval , Québec, Canada.
Oncology, Centre de Recherche du CHU de Québec-Université Laval , Québec, Canada.
Cell Cycle. 2020 Nov;19(22):2963-2981. doi: 10.1080/15384101.2020.1836441. Epub 2020 Oct 25.
The human adenovirus (Ad) type 2/5 early region 4 (E4) ORF4 protein (E4orf4) exerts a remarkable tumor cell-selective killing activity in mammalian cells. This indicates that E4orf4 can target tumor cell-defining features and is a unique tool to probe cancer cell vulnerabilities. Recently, we found that E4orf4, through an interaction with the polarity protein PAR3, subverts nuclear envelope (NE) remodeling processes in a tumor cell-selective manner. In this Perspective, we outline mechanical signals that modify nuclear dynamics and tumor cell behavior to highlight potential mechanisms for E4orf4's tumoricidal activity. Through an analysis of E4orf4's cellular targets, we define a protein subnetwork that comprises phosphatase systems interconnected to polarity protein hubs, which could contribute to enhanced NE plasticity. We infer that elucidating E4orf4's protein network at a functional level could uncover key mechanisms of NE remodeling that define the tumor cell phenotype.
人腺病毒（Ad）2/5 型早期区 4（E4）ORF4 蛋白（E4orf4）在哺乳动物细胞中具有显著的肿瘤细胞选择性杀伤活性。这表明 E4orf4 可以靶向肿瘤细胞的特征，是一种独特的工具，可以探测癌细胞的脆弱性。最近，我们发现 E4orf4 通过与极性蛋白 PAR3 的相互作用，以肿瘤细胞选择性的方式颠覆核膜（NE）重塑过程。在本观点中，我们概述了改变核动力学和肿瘤细胞行为的机械信号，以突出 E4orf4 杀瘤活性的潜在机制。通过对 E4orf4 的细胞靶标的分析，我们定义了一个包含磷酸酶系统相互连接到极性蛋白枢纽的蛋白质子网，这可能有助于增强 NE 的可塑性。我们推断，在功能水平上阐明 E4orf4 的蛋白质网络可能揭示定义肿瘤细胞表型的 NE 重塑的关键机制。
