CXCR4 in breast cancer: oncogenic role and therapeutic targeting.
CXCR4 in breast cancer: oncogenic role and therapeutic targeting.
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DOI：
10.2147/dddt.s84932
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Yao Q
中科院分区：
文献类型：
--
作者：
Xu C;Zhao H;Chen H;Yao Q
趋化因子是8-12 kDa的肽，其作为化学引诱细胞因子起作用，并参与细胞活化、分化和运输。趋化因子与特异性G蛋白偶联的七跨膜受体结合。趋化因子在多种细胞、生理和发育过程的调节中发挥重要作用。它们的异常表达可导致多种人类疾病，包括癌症。C-X-C趋化因子受体4型（CXCR 4），也称为融合蛋白或CD 184，是一种对基质衍生因子-1（SDF-1，也称为CXCL 12）具有特异性的α-趋化因子受体。CXCR 4属于七跨膜结构域异源三聚体G蛋白偶联受体的超家族，并且在各种类型的癌细胞的细胞表面上功能性表达。CXCR 4还在这些细胞的细胞增殖和迁移中起作用。最近，CXCR 4已被报道在包括乳腺癌在内的多种癌症的细胞存活、增殖、迁移以及转移中起重要作用。本文就CXCR 4在乳腺癌中的致癌作用及靶向药物的研究进展作一综述。此外，CXCR 4促血管生成的分子机制将进行审查。CXCR 4与CXCL 12的特异性结合和CXCR 4/CXCL 12复合物的激活使其成为乳腺癌防治的独特分子靶点。
Chemokines are 8–12 kDa peptides that function as chemoattractant cytokines and are involved in cell activation, differentiation, and trafficking. Chemokines bind to specific G-protein-coupled seven-span transmembrane receptors. Chemokines play a fundamental role in the regulation of a variety of cellular, physiological, and developmental processes. Their aberrant expression can lead to a variety of human diseases including cancer. C-X-C chemokine receptor type 4 (CXCR4), also known as fusin or CD184, is an alpha-chemokine receptor specific for stromal-derived-factor-1 (SDF-1 also called CXCL12). CXCR4 belongs to the superfamily of the seven transmembrane domain heterotrimeric G protein-coupled receptors and is functionally expressed on the cell surface of various types of cancer cells. CXCR4 also plays a role in the cell proliferation and migration of these cells. Recently, CXCR4 has been reported to play an important role in cell survival, proliferation, migration, as well as metastasis of several cancers including breast cancer. This review is mainly focused on the current knowledge of the oncogenic role and potential drugs that target CXCR4 in breast cancer. Additionally, CXCR4 proangiogenic molecular mechanisms will be reviewed. Strict biunivocal binding affinity and activation of CXCR4/CXCL12 complex make CXCR4 a unique molecular target for prevention and treatment of breast cancer.