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Int. J. Biochem. Cell Biol. · Feb 2018
ReviewThe good and bad faces of the CXCR4 chemokine receptor.
- Joaquin Teixidó, Mónica Martínez-Moreno, Marta Díaz-Martínez, and Silvia Sevilla-Movilla.
- Department of Cellular and Molecular Medicine, Centro de Investigaciones Biológicas (CSIC), 28040 Madrid, Spain. Electronic address: joaquint@cib.csic.es.
- Int. J. Biochem. Cell Biol. 2018 Feb 1; 95: 121-131.
AbstractChemokines are chemotactic cytokines that promote cell migration and activation under homeostatic and inflammatory conditions. Chemokines bind to seven transmembrane-spanning receptors that are coupled to heterotrimeric guanine nucleotide-binding (G) proteins, which are the responsible for intracellularly transmitting the activating signals for cell migration. Hematopoiesis, vascular development, lymphoid organ morphogenesis, cardiogenesis and neural differentiation are amongst the processes involving chemokine function. In addition, immune cell trafficking from bone marrow to blood circulation, and from blood and lymph to lymphoid and inflamed tissues, is tightly regulated by chemokines both under physiological conditions and also in autoimmune diseases. Furthermore, chemokine binding to their receptors stimulate trafficking to and positioning of cancer cells into target tissues and organs during tumour dissemination. The CXCL12 chemokine (also known as stromal-cell derived factor-1α, SDF-1α) plays key roles in hematopoiesis and lymphoid tissue architecture, in cardiogenesis, vascular formation and neurogenesis, as well as in the trafficking of solid and hematological cancer cell types. CXCL12 binds to the CXCR4 receptor, a multi-facetted molecule which tightly mirrors CXCL12 functions in homeostasis and disease. This review addresses the important roles of the CXCR4-CXCL12 axis in homeostasis, specially focusing in hematopoiesis, as well as it provides a picture of CXCR4 as mediator of cancer cell spreading, and a view of the available CXCR4 antagonists in different cancer types.Copyright © 2018 Elsevier Ltd. All rights reserved.
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