C-X-C motif chemokine ligand 12—C-X-C chemokine receptor type 4 signaling axis in cancer and the development of chemotherapeutic molecules
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 p...
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2024-05-01
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| Series: | Tzu Chi Medical Journal |
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| Online Access: | https://journals.lww.com/10.4103/tcmj.tcmj_52_24 |
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| author | Jui-Hung Yen Chun-Chun Chang Hao-Jen Hsu Chin-Hao Yang Hemalatha Mani Je-Wen Liou |
| author_facet | Jui-Hung Yen Chun-Chun Chang Hao-Jen Hsu Chin-Hao Yang Hemalatha Mani Je-Wen Liou |
| author_sort | Jui-Hung Yen |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-9ce66f22d15d40f990b7f887d4fd3bee |
| institution | DOAJ |
| issn | 1016-3190 2223-8956 |
| language | English |
| publishDate | 2024-05-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Tzu Chi Medical Journal |
| spelling | doaj-art-9ce66f22d15d40f990b7f887d4fd3bee2025-08-20T02:56:51ZengWolters Kluwer Medknow PublicationsTzu Chi Medical Journal1016-31902223-89562024-05-0136323123910.4103/tcmj.tcmj_52_24C-X-C motif chemokine ligand 12—C-X-C chemokine receptor type 4 signaling axis in cancer and the development of chemotherapeutic moleculesJui-Hung YenChun-Chun ChangHao-Jen HsuChin-Hao YangHemalatha ManiJe-Wen LiouChemokines 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.https://journals.lww.com/10.4103/tcmj.tcmj_52_24cancer progressionchemotherapeutic agentscxcl12cxcr4stromal cell-derived factor 1 |
| spellingShingle | Jui-Hung Yen Chun-Chun Chang Hao-Jen Hsu Chin-Hao Yang Hemalatha Mani Je-Wen Liou C-X-C motif chemokine ligand 12—C-X-C chemokine receptor type 4 signaling axis in cancer and the development of chemotherapeutic molecules Tzu Chi Medical Journal cancer progression chemotherapeutic agents cxcl12 cxcr4 stromal cell-derived factor 1 |
| title | C-X-C motif chemokine ligand 12—C-X-C chemokine receptor type 4 signaling axis in cancer and the development of chemotherapeutic molecules |
| title_full | C-X-C motif chemokine ligand 12—C-X-C chemokine receptor type 4 signaling axis in cancer and the development of chemotherapeutic molecules |
| title_fullStr | C-X-C motif chemokine ligand 12—C-X-C chemokine receptor type 4 signaling axis in cancer and the development of chemotherapeutic molecules |
| title_full_unstemmed | C-X-C motif chemokine ligand 12—C-X-C chemokine receptor type 4 signaling axis in cancer and the development of chemotherapeutic molecules |
| title_short | C-X-C motif chemokine ligand 12—C-X-C chemokine receptor type 4 signaling axis in cancer and the development of chemotherapeutic molecules |
| title_sort | c x c motif chemokine ligand 12 c x c chemokine receptor type 4 signaling axis in cancer and the development of chemotherapeutic molecules |
| topic | cancer progression chemotherapeutic agents cxcl12 cxcr4 stromal cell-derived factor 1 |
| url | https://journals.lww.com/10.4103/tcmj.tcmj_52_24 |
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