EphA6 promotes angiogenesis and prostate cancer metastasis and is associated with human prostate cancer progression.
EphA6 promotes angiogenesis and prostate cancer metastasis and is associated with human prostate cancer progression.
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EphA6 促进血管生成和前列腺癌转移，并与人类前列腺癌进展相关
DOI：
10.18632/oncotarget.4088
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发表时间：
2015-09-08
期刊：
影响因子：
--
通讯作者：
Guan M
中科院分区：
文献类型：
--
作者：
Li S;Ma Y;Xie C;Wu Z;Kang Z;Fang Z;Su B;Guan M
转移是前列腺癌（CaP）相关死亡的主要原因。我们研究了EphA 6表达和CaP转移的分子、病理和临床结果相关性。在亲本和转移性CaP细胞系中进行Eph受体（Ephs）及其肝配蛋白配体的表达谱分析。在Ephs和肝配蛋白中，只有EphA 6在转移性CaP细胞中始终过表达。在CaP自发转移小鼠模型中通过RNAi评估EphA 6的转移潜力。人PC-3 M细胞中EphA 6敲低导致体外侵袭降低和体内肺和淋巴结转移降低。此外，EphA 6的敲低降低了体外管形成和体内血管生成。与来自58名良性前列腺增生患者的良性组织相比，112名CaP肿瘤样品中EphA 6 mRNA表达更高。EphA 6的表达与前列腺癌的血管浸润、神经浸润、PSA水平及TNM分期呈正相关。此外，在EphA 6敲低细胞中的全基因组基因表达分析鉴定了一组差异调节的基因，包括PIK 3 IPA、AKT 1和EIF 5A 2，这些基因可能有助于EphA 6调节的癌症进展。这些发现将EphA 6鉴定为与CaP进展正相关的潜在新型转移基因。EphA 6可能是转移性CaP的治疗靶点。
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.