CXCL13 is androgen-responsive and involved in androgen induced prostate cancer cell migration and invasion.
CXCL13 is androgen-responsive and involved in androgen induced prostate cancer cell migration and invasion.
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CXCL13具有雄激素反应性，参与雄激素诱导的前列腺癌细胞迁移和侵袭
DOI：
10.18632/oncotarget.18387
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发表时间：
2017-08-08
期刊：
影响因子：
--
通讯作者：
Liu P
中科院分区：
文献类型：
--
作者：
Fan L;Zhu Q;Liu L;Zhu C;Huang H;Lu S;Liu P
雄激素受体（AR）是前列腺癌（PCa）发生发展的关键转录因子。然而，前列腺癌中AR作用的分子机制尚不十分清楚。CXCL 13又称B细胞趋化因子1（BCA-1），是CXC趋化因子家族的成员，与肿瘤转移密切相关。本研究表明，CXCL 13是一个雄激素反应基因，并参与AR诱导的PCa细胞迁移和侵袭。在临床标本中，CXCL 13在PCa组织中的表达明显高于癌旁正常组织。在培养物中，CXCL 13的表达在mRNA和蛋白质水平上都受到雄激素-AR轴的上调。此外，Chip-Seq测定鉴定了CXCL 13增强子处的典型雄激素应答元件（ARE），并且双荧光素酶报告基因测定揭示了ARE对雄激素高度应答，而ARE的突变消除了报告基因活性。其他染色质免疫沉淀（ChIP）试验也确定ARE呈现雄激素反应性。此外，CXCL 13通过增加PCa细胞中Cyclin B1水平促进G2/M期转变。功能研究表明，降低LNCaP细胞中的内源性CXCL 13表达在很大程度上削弱了雄激素-AR轴诱导的细胞迁移和侵袭。综上所述，我们的研究首次表明CXCL 13是AR靶基因，并参与AR介导的原发性PCa细胞迁移和侵袭。
Androgen receptor (AR) is a key transcription factor playing a critical role in prostate cancer (PCa) initiation and progression. However, the molecular mechanisms of AR action in prostate cancer are not very clear. CXCL13, known as B cell attracting chemokine1 (BCA-1), is a member of CXC chemokine family and relevant to cancer metastasis. This study shows that CXCL13 is an androgen-responsive gene and involved in AR-induced PCa cell migration and invasion. In clinical specimens, expression of CXCL13 in PCa tissues is markedly higher than that in adjacent normal tissues. In cultures, expression of CXCL13 is up-regulated by androgen-AR axis at both mRNA and protein levels. Furthermore, Chip-Seq assay identifies canonical androgen responsive elements (ARE) at CXCL13 enhancer and dual-luciferase reporter assays reveals that the ARE is highly responsive to androgen while mutations of the ARE abolish the reporter activity. Additional chromatin immunoprecipitation (ChIP) assays also identify that the ARE presents androgen responsiveness. In addition, CXCL13 promotes G2/M phase transition by increasing Cyclin B1 levels in PCa cells. Functional studies demonstrate that reducing endogenous CXCL13 expression in LNCaP cells largely weakens androgen-AR axis induced cell migration and invasion. Taken together, our study implicates for the first time that CXCL13 is an AR target gene and involved in AR-mediated cell migration and invasion in primary PCa.
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影响因子：
37.3
作者：
El Haibi CP;Sharma PK;Singh R;Johnson PR;Suttles J;Singh S;Lillard JW Jr
通讯作者：
Lillard JW Jr
影响因子：
8.5
作者：
El-Haibi CP;Singh R;Sharma PK;Singh S;Lillard JW Jr
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通讯作者：
Atanackovic, D.
影响因子：
8
作者：
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Burger, JA
影响因子：
4.8
作者：
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