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

被引:2
作者
Yen, Jui-Hung [1 ]
Chang, Chun-Chun [2 ,3 ]
Hsu, Hao-Jen [4 ]
Yang, Chin-Hao [5 ]
Mani, Hemalatha [5 ]
Liou, Je-Wen [3 ,4 ,5 ]
机构
[1] Tzu Chi Univ, Dept Mol Biol & Human Genet, Hualien, Taiwan
[2] Hualien Tzu Chi Hosp, Buddhist Tzu Chi Med Fdn, Dept Lab Med, Hualien, Taiwan
[3] Tzu Chi Univ, Dept Lab Med & Biotechnol, Hualien, Taiwan
[4] Tzu Chi Univ, Dept Biomed Sci & Engn, Hualien, Taiwan
[5] Tzu Chi Univ, Sch Med, Dept Biochem, 701 Zhongyang Rd,Sect 3, Hualien, Taiwan
来源
TZU CHI MEDICAL JOURNAL | 2024年 / 36卷 / 03期
关键词
Cancer progression; Chemotherapeutic agents; CXCL12; CXCR4; Stromal cell-derived factor 1; LYMPH-NODE METASTASIS; G-BETA-GAMMA; NF-KAPPA-B; CXCR4; EXPRESSION; CELL-SURVIVAL; IMMUNE SURVEILLANCE; DOWN-REGULATION; BINDING-SITE; ACTIVATION; BREAST;
D O I
10.4103/tcmj.tcmj_52_24
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:231 / 239
页数:9
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