LASP1 is a HIF1α target gene critical for metastasis of pancreatic cancer.
LASP1 is a HIF1α target gene critical for metastasis of pancreatic cancer.
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LASP1 是 HIF1α 靶基因，对胰腺癌转移至关重要
DOI：
10.1158/0008-5472.can-14-2040
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发表时间：
2015-01-01
期刊：
影响因子：
11.2
通讯作者：
Hao J
中科院分区：
文献类型：
--
作者：
Zhao T;Ren H;Li J;Chen J;Zhang H;Xin W;Sun Y;Sun L;Yang Y;Sun J;Wang X;Gao S;Huang C;Zhang H;Yang S;Hao J
LASP 1是一种与癌细胞中肌动蛋白组装动力学相关的肌动蛋白结合蛋白。在这里，我们报告LASP 1在胰腺导管腺癌（PDAC）中过表达，它促进了浸润和转移。我们发现，LASP 1在PDAC细胞中的过表达是由HIF-1α通过直接结合LASP 1启动子中的缺氧反应元件介导的。HIF-1α在体外刺激PDAC细胞和体内小鼠肿瘤异种移植物中的LASP 1表达。临床上，LASP 1在PDAC患者标本中的过表达与淋巴结转移和总生存率显著相关。总之，我们的研究结果将LASP 1定义为HIF-1α上调的直接靶基因，HIF-1α上调对PDAC的转移进展至关重要。
LASP1 is an actin-binding protein associated with actin assembly dynamics in cancer cells. Here we report that LASP1 is overexpressed in pancreatic ductal adenocarcinoma (PDAC) where it promotes invasion and metastasis. We found that LASP1 overexpression in PDAC cells was mediated by HIF-1α through direct binding to a hypoxia response element in the LASP1 promoter. HIF-1α stimulated LASP1 expression in PDAC cells in vitro and mouse tumor xenografts in vivo. Clinically, LASP1 overexpression in PDAC patient specimens was associated significantly with lymph node metastasis and overall survival. Overall, our results defined LASP1 as a direct target gene for HIF-1α upregulation that is critical for metastatic progression of PDAC.