The Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor: Lessons on dysregulated angiogenesis from a viral oncogene.
The Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor: Lessons on dysregulated angiogenesis from a viral oncogene.
复制标题
DOI：
10.1002/jcb.22524
复制
发表时间：
2010-05
影响因子：
4
通讯作者：
Montaner, Silvia
中科院分区：
文献类型：
--
作者：
Jham, Bruno C.;Montaner, Silvia
关键词：
肿瘤病毒可以通过克服细胞防御机制并促进受感染细胞的不受控制的增殖来诱导细胞转化。为此，功能相关的病毒癌基因在不同的病毒中进化，以超越关键的增殖和存活细胞内途径，从而确保有效的病毒复制并促进肿瘤形成。事实上，病毒癌基因的研究已成为揭示这些基本细胞过程的基本见解的有力工具。在这方面，卡波西肉瘤相关疱疹病毒（KSHV或HHV8）是卡波西肉瘤（KS）的病原体，是致癌病毒的典型模型，其基因组内包含与细胞增殖和凋亡调节有关的细胞基因的几个同源物。然而，现在新出现的证据表明，编码病毒 G 蛋白偶联受体 (vGPCR) 的单个 KSHV 基因 ORF74 对于 KS 发育至关重要。这种病毒受体仅在 KS 病变内的一小部分细胞中表达，通过自分泌和旁分泌机制诱导肿瘤发生。事实上，多个实验室的工作表明，vGPCR 可以促进细胞增殖、增强细胞存活、调节细胞迁移、刺激血管生成以及招募表达细胞和邻近（旁观者）细胞中的炎症细胞。对这种强大的病毒癌基因的检查可能会揭示治疗 KS 患者的新靶点，并最终为 GPCR（特别是趋化因子受体）如何促进血管生成和肿瘤发生提供独特的视角。
Tumor viruses can induce cell transformation by overcoming cellular defense mechanisms and promoting the ungoverned proliferation of infected cells. To this end, functionally related viral oncogenes have evolved in disparate viruses to override key proliferative and survival intracellular pathways, thus assuring efficient viral replication and contributing to tumor formation. Indeed, the study of viral oncogenes has been a powerful tool for disclosing fundamental insights into these basic cellular processes. In this regard, the Kaposi’s sarcoma-associated Herpesvirus (KSHV or HHV8), the etiological agent of Kaposi’s sarcoma (KS), is an exemplary model of an oncogenic virus that includes within its genome several homologues of cellular genes implicated in the regulation of cell proliferation and apoptosis. However, emerging evidence now points to a single KSHV gene, ORF74, encoding for the viral G protein-coupled receptor (vGPCR), as essential for KS development. Expressed in only a fraction of cells within KS lesions, this viral receptor induces tumorigenesis through both autocrine and paracrine mechanisms. Indeed, work from several labs has demonstrated that vGPCR can promote cell proliferation, enhance cell survival, modulate cell migration, stimulate angiogenesis, and recruit inflammatory cells, both in expressing cells, as well as in neighboring (bystander) cells. Examination of this powerful viral oncogene may expose novel targets for the treatment of patients with KS and could ultimately provide a unique perspective into how GPCRs, and specifically chemokine receptors, contribute to angiogenesis and tumorigenesis.
登录
查看更多内容
DOI：
10.1073/pnas.011528498
发表时间：
2001-01-02
影响因子：
11.1
作者：
Aoki, M;Blazek, E;Vogt, PK
通讯作者：
Vogt, PK
DOI：
10.1073/pnas.96.8.4546
发表时间：
1999-04-13
影响因子：
11.1
作者：
Dupin, N;Fisher, C;Boshoff, C
通讯作者：
Boshoff, C
DOI：
10.1084/jem.58.5.607
发表时间：
1933-10-31
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Shope RE;Hurst EW
通讯作者：
Hurst EW
影响因子：
10.5
作者：
Inoki, K;Li, Y;Guan, KL
通讯作者：
Guan, KL
影响因子：
3.7
作者：
Bottero, Virginie;Sharma-Walia, Neelam;Kerur, Nagaraj;Paul, Arun George;Sadagopan, Sathish;Cannon, Mark;Chandran, Bala
通讯作者：
Chandran, Bala