Expression profiling identifies new function of collapsin response mediator protein 4 as a metastasis-suppressor in prostate cancer

Expression profiling identifies new function of collapsin response mediator protein 4 as a metastasis-suppressor in prostate cancer
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表达谱鉴定了塌陷素反应介导蛋白 4 作为前列腺癌转移抑制剂的新功能

DOI:
10.1038/onc.2010.213
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发表时间:
2010-08-12
期刊:
影响因子:
8
通讯作者:
Li, B-Y
Li, B-Y
中科院分区:
医学1区
文献类型:
--
作者:
Gao, X.;Pang, J.;Li, B-Y

文献摘要

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转移是癌症死亡的主要原因,但导致转移的机制知之甚少。我们使用蛋白质组学方法筛选转移相关蛋白,发现前列腺素反应介导蛋白-4(CRMP 4)表达与前列腺癌(PCa)的淋巴结转移呈负相关。随后的体外和体内研究表明,CRMP 4的过表达不仅抑制了PCa细胞的侵袭能力,而且在动物模型中强烈抑制了肿瘤转移。此外,CRMP 4基因的启动子区域内的CpG岛的甲基化负责CRMP 4表达的下调。因此,在这项研究中,我们显示了CRMP 4作为PCa转移抑制剂的新功能。这些发现为这种最常见的男性癌症的转移和治疗潜力提供了新的机制见解。
Metastasis is the chief cause of mortality from cancer, but the mechanisms leading to metastasis are poorly understood. We used a proteomics approach to screen for metastasis-associated proteins and found that collapsin response mediator protein-4 (CRMP4) expression was inversely associated with the lymph node metastasis of prostate cancer (PCa). Subsequent in vitro and in vivo studies revealed that overexpression of CRMP4 not only suppressed the invasion ability of PCa cells, but also strongly inhibited tumor metastasis in an animal model. Furthermore, methylation of a CpG island within the promoter region of the CRMP4 gene is responsible for downregulation of CRMP4 expression. Thus, in this study, we show new function of CRMP4 as a metastasis-suppressor in PCa. The findings provide new mechanistic insights into metastasis and therapeutic potential for this most common male cancer.