C5b-9和RGC-32在癌症中的作用
补体系统代表先天免疫的有效库,以及先天免疫和适应性免疫之间的接口。补体系统的激活最终随着C5b-9末端补体复合物在细胞膜上的组装而结束,从而诱导靶细胞裂解。将该事件序列转化为恶性环境,传统上已赋予C5b-9严格的抗肿瘤作用,与抗体依赖性肿瘤细胞溶解协同作用。然而,在最近几十年中,大量证据修改了这种观点,突出了C5b-9的促肿瘤特性。分解C5b-9通过激活信号转导途径(例如,Gi蛋白/磷脂酰肌醇3-激酶(PI3K)/ Akt激酶和Ras / Raf1 / ERK1)并调节癌症相关转录因子的激活来诱导细胞周期进程,同时屏蔽恶性肿瘤细胞凋亡。 C5b-9还诱导补体应答基因(RGC)-32,该基因通过激活Akt和CDC2激酶有助于细胞周期调控。 RGC-32在肿瘤细胞中表达并在癌症中起双重作用,通过支持恶性肿瘤的起始,进展,侵袭,转移和血管生成而充当肿瘤启动子,或者起抑癌作用。在这篇综述中,我们提供了描述C5b-9及其效应物RGC-32在癌症中的多方面作用的最新数据。**
Role of C5b-9 and RGC-32 in Cancer
The complement system represents an effective arsenal of innate immunity as well as an interface between innate and adaptive immunity. Activation of the complement system culminates with the assembly of the C5b-9 terminal complement complex on cell membranes, inducing target cell lysis. Translation of this sequence of events into a malignant setting has traditionally afforded C5b-9 a strict antitumoral role, in synergy with antibody-dependent tumor cytolysis. However, in recent decades, a plethora of evidence has revised this view, highlighting the tumor-promoting properties of C5b-9. Sublytic C5b-9 induces cell cycle progression by activating signal transduction pathways (e.g., Gi protein/ phosphatidylinositol 3-kinase (PI3K)/Akt kinase and Ras/Raf1/ERK1) and modulating the activation of cancer-related transcription factors, while shielding malignant cells from apoptosis. C5b-9 also induces Response Gene to Complement (RGC)-32, a gene that contributes to cell cycle regulation by activating the Akt and CDC2 kinases. RGC-32 is expressed by tumor cells and plays a dual role in cancer, functioning as either a tumor promoter by endorsing malignancy initiation, progression, invasion, metastasis, and angiogenesis, or as a tumor suppressor. In this review, we present recent data describing the versatile, multifaceted roles of C5b-9 and its effector, RGC-32, in cancer.
pmid: 31156630 Front Immunol 影响因子: 4.716 发表日期: 20190101 官网 免费下载
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