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配体 CX3CL1 及其受体 CX3CR1 在癌症中的结构与功能

英文原题:Structure and Function of Ligand CX3CL1 and its Receptor CX3CR1 in Cancer.

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Structure and Function of Ligand CX3CL1 and its Receptor CX3CR1 in Cancer.

PubMed 2022/01/01(内容时间) Curr Med Chem Q2 · IF 3.2(JCR 2025)

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中文摘要

C-X3-C基序趋化因子配体(CX3CL)1(也称为Fractalkine)及其受体CX3CR1(也称为G蛋白偶联受体13)表达于多种不同细胞的膜上,如上皮细胞、树突状细胞、平滑肌细胞和神经元。CX3CR1主要表达于单核细胞、巨噬细胞、树突状细胞、T细胞和NK 细胞。CX3CL1与CX3CR1的结合诱导与该受体相关的异三聚体G蛋白活化。此外,它还触发MAPK和AKT信号通路,这些通路在肿瘤生物学中发挥重要作用。在机制上,CX3CL1-CX3CR1轴通过将NK细胞和T细胞等抗肿瘤免疫细胞募集到肿瘤微环境中来控制肿瘤生长,从而发挥抗肿瘤作用。另一方面,越来越多的证据表明,CX3CL1-CX3CR1轴也会激活促肿瘤反应。本综述将聚焦于CX3CL1和CX3CR1独特的结构生物学特征、它们在肿瘤炎症反应中的相互作用以及抗肿瘤效应,从而突出可能的潜在治疗靶点。

展开英文摘要原文

The C-X3-C motif chemokine ligand (CX3CL)1 (also known as Fractalkine) and its receptor CX3CR1 (also known as G-protein coupled receptor 13) are expressed on the membranes of many different cells such as epithelial cells, dendritic cells, smooth muscle cells, and neurons. CX3CR1 is primarily expressed on monocytes, macrophages, dendritic cells, T cells, and natural killer cells. The binding of CX3CL1 to CX3CR1 induces the activation of heterotrimeric G proteins associated with this receptor.

In addition, it triggers the signal pathways of MAPK and AKT, which play essential roles in tumour biology.

Mechanistically, the CX3CL1-CX3CR1 axis has an antitumour role by recruiting antitumoural immune cells such as NK cells and T cells into the tumour microenvironment to control tumour growth. On the other hand, accumulated evidence indicates that the CX3CL1-CX3CR1 axis also activates a pro-tumoral response. This review will focus on the unique structural biology features of CX3CL1 and CX3CR1, their interactions in tumour inflammatory response, and antitumour effects, which highlights possible potential therapeutic targets.

论文信息

作者
Lu X
单位
The Mary and Garry Weston Molecular Immunology Laboratory, Thrombosis Research Institute, London, SW3 6LR, United Kingdom.United Kingdom
文献类型
综述
期刊
Current medicinal chemistry2022
原文标识
PubMed 35770395 · DOI 10.2174/0929867329666220629140540