title: CXCR4 in breast cancer: oncogenic role and therapeutic targeting.
abstract: 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.
authors.affiliation: First Clinical College of Zhejiang Chinese Medical University, Hangzhou, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Xu
authors.affiliation: First Clinical College of Zhejiang Chinese Medical University, Hangzhou, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.affiliation: First Clinical College of Zhejiang Chinese Medical University, Hangzhou, People's Republic of China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Integrated Traditional Chinese and Western Medicine, Zhejiang Cancer Hospital, Hangzhou, People's Republic of China ; Key Laboratory of Integrated Traditional Chinese and Western Medicine, Zhejiang Cancer Hospital, Hangzhou, People's Republic of China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Yao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D005260:Female; D006801:Humans; D058990:Molecular Targeted Therapy; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; C527276:CXCR4 protein, human; D019718:Receptors, CXCR4
keywords: CXCR4; angiogenesis; breast cancer; chemokine; drug target