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首页> 外文期刊>Cellular Signalling >DAB2IP regulates EMT and metastasis of prostate cancer through targeting PROX1 transcription and destabilizing HIF1 alpha protein
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DAB2IP regulates EMT and metastasis of prostate cancer through targeting PROX1 transcription and destabilizing HIF1 alpha protein

机译：DAB2IP通过靶向PROX1转录和破坏HIF1α蛋白来调节前列腺癌的EMT和转移

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摘要

Prospero-related homeobox 1 (PROX1) is an essential regulator in lymphangiogenesis and has been implicated in both oncogenic and tumor-suppressive functions in many types of human cancers. However, the role of PROX1 in prostate cancer (PCa) remains poorly understood. In this study, based on different PCa cell lines and knockout mice, we showed that PROX1 could be suppressed by DAB2IP, a novel member of the Ras GTPase-activating protein family and a critical player in control of epithelial-mesenchymal transition (EMT) and PCa metastasis. Mechanistically, PROX1 overexpression in DAB2IP-deficient PCa cells could enhance the accumulation of HIF1 alpha protein by inhibiting ubiquitin pathway and then consequently induce an EMT response, which is characterized by repression of E-cadherin, up-regulation of vimentin and matrix metallopeptidases (MMPs) and enhancement of cell migration. Together, our data provides a new insight into mechanism that DAB2IP regulates EMT and PCa metastasis, especially points out the potential roles of its downstream PROX1/HIF1 alpha signaling in a unique non skeletal metastasis of PCa. (C) 2016 Elsevier Inc. All rights reserved.
机译：与Prospero相关的同源盒1（PROX1）是淋巴管生成中必不可少的调节剂，并且与多种类型的人类癌症中的致癌和肿瘤抑制功能有关。但是，对PROX1在前列腺癌（PCa）中的作用仍然知之甚少。在这项研究中，基于不同的PCa细胞系和基因敲除小鼠，我们显示PROX1可以被DAB2IP抑制，DAB2IP是Ras GTPase激活蛋白家族的新成员，并且是控制上皮-间质转化（EMT）和PCa转移。从机理上讲，在缺乏DAB2IP的PCa细胞中，PROX1的过表达可以通过抑制泛素途径来增强HIF1α蛋白的积累，然后诱导EMT响应，其特征是抑制E-钙粘蛋白，上调波形蛋白和基质金属肽酶（MMP） ）并增强细胞迁移。总之，我们的数据为DAB2IP调节EMT和PCa转移的机制提供了新的见解，特别指出了其下游PROX1 / HIF1 alpha信号在PCa独特的非骨骼转移中的潜在作用。 （C）2016 Elsevier Inc.保留所有权利。

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