Under physiological conditions, CXCL12 modulates cell proliferation, survival, angiogenesis, and migration mainly through CXCR4. Interestingly, the newly discovered receptor CXCR7 for CXCL12 is highly expressed in many tumor cells as well as tumor-associated blood vessels, although the level of CXCR7 in normal blood cells is low. Recently, many studies have suggested that CXCR7 promotes cell growth and metastasis in various cancers, including lymphoma and leukemia, hepatocecullar, ovarian, colorectal, breast and lung cancer. Compared to CXCR4, CXCR7 is a non-classical GPCR that is unable to activate G proteins. The function of CXCR7 is generally considered to be mediated by: (a) recruiting beta-arrestin-2; (b) heterodimerizing with CXCR4; and (c) acting as a "scavenger" of CXCL12, thus lowering the level of CXCL12 to weaken the activity of CXCR4. However, the crosstalk between CXCL12/CXCR7/CXCR4 and other signaling pathways (such as the p38 MAPK pathway, the PI3K/mTOR pathway, the STAT3 signaling, and metalloproteinases MMP-9 and MMP-2) is more complicated. The function of CXCR7 is also involved in modulating tumor microenvironment, tumor cell migration and apoptosis. Understanding these complex interactions will provide insight in drug design targeting the CXCR7 as potential anticancer therapy.
基金：
National Natural Science
Foundation of China 81271420 and 81471936. HAZ would
like to thank the financial support from the Faculty Development Fellowship from the University of Nebraska at
Omaha (2014-2015).
第一作者机构：[1]Wuhan Univ, Coll Life Sci, State Key Lab Virol, Wuhan 430072, Peoples R China[2]Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Ctr Neuroimmunol & Regenerat Therapy, Shanghai 200072, Peoples R China
通讯作者：
通讯机构：[4]Shanghai Jiao Tong Univ, Sch Med, Tongren Hosp, Div Cardiol, 1111 Xianxia Rd, Shanghai 200336, Peoples R China[5]Univ Nebraska, Dept Chem, DSC 362,6001 Dodge St, Omaha, NE 68182 USA[6]Univ Nebraska Med Ctr, Fred & Pamela Buffett Canc Ctr, 986805 Nebraska Med Ctr, Omaha, NE 68198 USA[*1]DSC 362, Department of Chemistry, The University of Nebraska at Omaha, 6001 Dodge Street, Omaha, Nebraska 68182 U.S.A.[*2]Cardiology Division of Cardiology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 1111 Xianxia Road, Shanghai, P.R. China 200336.
推荐引用方式(GB/T 7714)：
Xu Dongsheng,Li Rongshi,Wu Jianguo,et al.Drug Design Targeting the CXCR4/CXCR7/CXCL12 Pathway[J].CURRENT TOPICS IN MEDICINAL CHEMISTRY.2016,16(13):1441-1451.doi:10.2174/1568026615666150915120218.
APA：
Xu, Dongsheng,Li, Rongshi,Wu, Jianguo,Jiang, Li&Zhong, Haizhen A..(2016).Drug Design Targeting the CXCR4/CXCR7/CXCL12 Pathway.CURRENT TOPICS IN MEDICINAL CHEMISTRY,16,(13)
MLA：
Xu, Dongsheng,et al."Drug Design Targeting the CXCR4/CXCR7/CXCL12 Pathway".CURRENT TOPICS IN MEDICINAL CHEMISTRY 16..13(2016):1441-1451
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