CXCL12 (SDF-1)/CXCR4 pathway in cancer.
Chemokines, small proinflammatory chemoattractant cytokines that bind to specific G-protein-coupled seven-span transmembrane receptors, are major regulators of cell trafficking and adhesion. The chemokine CXCL12 [stromal cell-derived factor-1 (SDF-1)] binds primarily to CXC receptor 4 (CXCR4; CD184). The binding of CXCL12 to CXCR4 induces intracellular signaling through several divergent pathways initiating signals related to chemotaxis, cell survival and/or proliferation, increase in intracellular calcium, and gene transcription. CXCR4 is expressed on multiple cell types including lymphocytes, hematopoietic stem cells, endothelial and epithelial cells, and cancer cells. The CXCL12/CXCR4 axis is involved in tumor progression, angiogenesis, metastasis, and survival. This pathway is a target for therapeutics that can block the CXCL12/CXCR4 interaction or inhibit downstream intracellular signaling.
Teicher
Beverly A
BA
Genzyme Corporation, Framingham, Massachusetts 01701-9322, USA. Beverly.Teicher@Genzyme.com
Fricker
Simon P
SP
D054377:Chemokine CXCL12 / Q000378:metabolism*; D016503:Drug Delivery Systems; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000235:genetics
D054377:Chemokine CXCL12; D019718:Receptors, CXCR4