title: Role of chemokine receptor CXCR7 in bladder cancer progression.
abstract: Bladder cancer is one of the most common tumors of the genitourinary tract; however, the molecular events underlying growth and invasion of the tumor remain unclear. Here, role of the CXCR7 receptor in bladder cancer was further explored. CXCR7 protein expression was examined using high-density tissue microarrays. Expression of CXCR7 showed strong epithelial staining that correlated with bladder cancer progression. In vitro and in vivo studies in bladder cancer cell lines suggested that alterations in CXCR7 expression were associated with the activities of proliferation, apoptosis, migration, invasion, angiogenesis and tumor growth. Moreover, CXCR7 expression was able to regulate expression of the proangiogenic factors IL-8 or VEGF, which may involve in the regulation of tumor angiogenesis. Finally, we found that signaling by the CXCR7 in bladder cancer cells activates AKT, ERK and STAT3 pathways. The AKT and ERK pathways may reciprocally regulate, which are responsible for in vitro and in vivo epithelial to mesenchymal transition (EMT) process of bladder cancer. Simultaneously targeting the two pathways by using U0126 and LY294002 inhibitors or using CCX733, a selective CXCR7 antagonist drastically reduced CXCR7-induced EMT process. Taken together, our data show for the first time that CXCR7 plays a role in the development of bladder cancer. Targeting CXCR7 or its downstream-activated AKT and ERK pathways may prove beneficial to prevent metastasis and provide a more effective therapeutic strategy for bladder cancer.
authors.affiliation: Department of Biochemistry and Molecular & Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
authors.forename: Mingang
authors.initials: M
authors.lastname: Hao
authors.forename: Jianghua
authors.initials: J
authors.lastname: Zheng
authors.forename: Kailin
authors.initials: K
authors.lastname: Hou
authors.forename: Jinglong
authors.initials: J
authors.lastname: Wang
authors.forename: Xiaosong
authors.initials: X
authors.lastname: Chen
authors.forename: Xiaojiong
authors.initials: X
authors.lastname: Lu
authors.forename: Junjie
authors.initials: J
authors.lastname: Bo
authors.forename: Chen
authors.initials: C
authors.lastname: Xu
authors.forename: Kunwei
authors.initials: K
authors.lastname: Shen
authors.forename: Jianhua
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D016513:Mice, SCID; D009025:Morpholines / Q000494:pharmacology; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering; D054387:Receptors, CXCR / Q000235:genetics / Q000502:physiology*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C501896:ACKR3 protein, human; D002070:Butadienes; D002867:Chromones; D016209:Interleukin-8; D009025:Morpholines; D009570:Nitriles; D034741:RNA, Small Interfering; D054387:Receptors, CXCR; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C113580:U 0126; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D051057:Proto-Oncogene Proteins c-akt