期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 388, 期 2, 页码 199-204出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2009.07.153
关键词
CXCR4; CXCL12; Chemokines; Chemokine receptors; Adhesion; Invasion; PI3K gamma; G proteins
资金
- Comunidad de Madrid (Spain) [CCG08-CSIC/SAL-33774, 3477]
- European Union [UE-518167]
- Spanish Ministry of Health [PI050964]
- CSIC [PIE-200720I031]
Tumor dissemination is a complex process, in which certain steps resemble those in leukocyte homing. Specific chemokine/chemokine receptor pairs have important roles in both processes. CXCL12/CXCR4 is the most commonly expressed chemokine/chemokine receptor pair in human cancers, in which it regulates cell adhesion, extravasation, metastatic colonization, angiogenesis, and proliferation. All of these processes require activation of signaling pathways that include G proteins, phosphatidylinositol-3 kinase (PI3K), JAK kinases, Rho GTPases, and focal adhesion-associated proteins. We analyzed these pathways in a human melanoma cell line in response to CXCL12 stimulation, and found that PI3K gamma regulates tumor cell adhesion through mechanisms different from those involved in cell invasion. Our data indicate that, following CXCR4 activation after CXCL12 binding, the invasion and adhesion processes are regulated differently by distinct downstream events in these signaling cascades. (C) 2009 Elsevier Inc. All rights reserved.
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