title: EphA6 promotes angiogenesis and prostate cancer metastasis and is associated with human prostate cancer progression.
abstract: Metastasis is the primary cause of prostate cancer (CaP)-related death. We investigate the molecular, pathologic and clinical outcome associations of EphA6 expression and CaP metastasis. The expression profiling of Eph receptors (Ephs) and their ephrin ligands was performed in parental and metastatic CaP cell lines. Among Ephs and ephrins, only EphA6 is consistently overexpressed in metastatic CaP cells. Metastatic potential of EphA6 is assessed by RNAi in a CaP spontaneous metastasis mouse model. EphA6 knock-down in human PC-3M cells causes decreased invasion in vitro and reduced lung and lymph node metastasis in vivo. In addition, knock-down of EphA6 decreases tube formation in vitro and angiogenesis in vivo. EphA6 mRNA expression is higher in 112 CaP tumor samples compared with benign tissues from 58 benign prostate hyperplasia patients. Positive correlation was identified between EphA6 expression and vascular invasion, neural invasion, PSA level, and TNM staging in CaP cases. Further, genome-wide gene expression analysis in EphA6 knock-down cells identified a panel of differentially regulated genes including PIK3IPA, AKT1, and EIF5A2, which could contribute to EphA6-regulated cancer progression. These findings identify EphA6 as a potentially novel metastasis gene which positively correlates with CaP progression. EphA6 may be a therapeutic target in metastatic CaP.
authors.affiliation: Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China.
authors.forename: Shibao
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
authors.forename: Yingyu
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Biomedical Research Institute, Shenzhen-PKU-HKUST Medical Center, Shenzhen, Guangdong 518036, China.
authors.forename: Chongwei
authors.initials: C
authors.lastname: Xie
authors.affiliation: Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Kang
authors.affiliation: Department of Urology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China.
authors.forename: Zujun
authors.initials: Z
authors.lastname: Fang
authors.affiliation: Xinxiang Key Lab of Translational Cancer Research, The Third Affiliated Hospital, Xinxiang Medical University, Xinxiang, Henan 453003, China.|Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York, Buffalo, NY 14214, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Su
authors.affiliation: Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Guan
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D018450:Disease Progression; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D036124:Receptor, EphA6 / Q000378:metabolism*; D014162:Transfection
chemical_list: D036124:Receptor, EphA6
keywords: Eph; EphA6; ephrin; metastasis; prostate cancer