C-X-C motif chemokine ligand 12-C-X-C chemokine receptor type 4 signaling axis in cancer and the development of chemotherapeutic molecules.

IF 1.4 Q2 MEDICINE, GENERAL & INTERNAL Tzu Chi Medical Journal Pub Date : 2024-05-27 eCollection Date: 2024-07-01 DOI:10.4103/tcmj.tcmj_52_24
Jui-Hung Yen, Chun-Chun Chang, Hao-Jen Hsu, Chin-Hao Yang, Hemalatha Mani, Je-Wen Liou
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Abstract

Chemokines are small, secreted cytokines crucial in the regulation of a variety of cell functions. The binding of chemokine C-X-C motif chemokine ligand 12 (CXCL12) (stromal cell-derived factor 1) to a G-protein-coupled receptor C-X-C chemokine receptor type 4 (CXCR4) triggers downstream signaling pathways with effects on cell survival, proliferation, chemotaxis, migration, and gene expression. Intensive and extensive investigations have provided evidence suggesting that the CXCL12-CXCR4 axis plays a pivotal role in tumor development, survival, angiogenesis, metastasis, as well as in creating tumor microenvironment, thus implying that this axis is a potential target for the development of cancer therapies. The structures of CXCL12 and CXCR4 have been resolved with experimental methods such as X-ray crystallography, NMR, or cryo-EM. Therefore, it is possible to apply structure-based computational approaches to discover, design, and modify therapeutic molecules for cancer treatments. Here, we summarize the current understanding of the roles played by the CXCL12-CXCR4 signaling axis in cellular functions linking to cancer progression and metastasis. This review also provides an introduction to protein structures of CXCL12 and CXCR4 and the application of computer simulation and analysis in understanding CXCR4 activation and antagonist binding. Furthermore, examples of strategies and current progress in CXCL12-CXCR4 axis-targeted development of therapeutic anticancer inhibitors are discussed.

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癌症中的 C-X-C motif 趋化因子配体 12-C-X-C 趋化因子受体 4 型信号轴与化疗分子的开发。
趋化因子是一种小型分泌型细胞因子,对调节多种细胞功能至关重要。趋化因子 C-X-C 矩阵趋化因子配体 12(CXCL12)(基质细胞衍生因子 1)与 G 蛋白偶联受体 C-X-C 趋化因子受体 4 型(CXCR4)结合,触发下游信号通路,对细胞存活、增殖、趋化、迁移和基因表达产生影响。大量深入的研究表明,CXCL12-CXCR4 轴在肿瘤发生、存活、血管生成、转移以及肿瘤微环境的形成过程中起着关键作用,这意味着该轴是开发癌症疗法的潜在靶点。CXCL12 和 CXCR4 的结构已通过 X 射线晶体学、核磁共振或低温电子显微镜等实验方法得到解析。因此,应用基于结构的计算方法来发现、设计和改造用于癌症治疗的治疗分子成为可能。在此,我们总结了目前对 CXCL12-CXCR4 信号轴在与癌症进展和转移相关的细胞功能中所起作用的理解。本综述还介绍了 CXCL12 和 CXCR4 的蛋白质结构,以及计算机模拟和分析在理解 CXCR4 激活和拮抗剂结合方面的应用。此外,还讨论了针对 CXCL12-CXCR4 轴开发治疗性抗癌抑制剂的策略实例和当前进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Tzu Chi Medical Journal
Tzu Chi Medical Journal MEDICINE, GENERAL & INTERNAL-
CiteScore
3.40
自引率
0.00%
发文量
44
审稿时长
13 weeks
期刊介绍: The Tzu Chi Medical Journal is the peer-reviewed publication of the Buddhist Compassion Relief Tzu Chi Foundation, and includes original research papers on clinical medicine and basic science, case reports, clinical pathological pages, and review articles.
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