HIF-3α Promotes Metastatic Phenotypes in Pancreatic Cancer by Transcriptional Regulation of the RhoC-ROCK1 Signaling Pathway
HIF-3α Promotes Metastatic Phenotypes in Pancreatic Cancer by Transcriptional Regulation of the RhoC-ROCK1 Signaling Pathway
复制标题
HIF-3alpha 通过 RhoC-ROCK1 信号通路的转录调节促进胰腺癌的转移表型。
DOI：
10.1158/1541-7786.mcr-17-0256
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发表时间：
2018-01-01
影响因子：
5.2
通讯作者：
Jiang, Jianxin
中科院分区：
文献类型：
--
作者：
Zhou, Xianfei;Guo, Xingjun;Jiang, Jianxin
缺氧有助于胰腺癌的进展，促进其生长和侵袭。以往的研究主要集中在缺氧诱导因子-1 α (HIF-1 α)和HIF-2 α （HIF1A和EPAS1）作为胰腺癌中主要的缺氧相关转录因子。然而，HIF-3 α (HIF3A)的作用尚未被研究。因此，HIF-1 α、HIF-2 α和HIF-3 α在常氧和缺氧条件下的表达水平被测量。此外，我们在人胰腺癌组织标本中检测了HIF-3 α的表达，并在体外和体内研究了HIF-3 α表达改变对细胞侵袭和迁移的影响及其潜在机制。缺氧条件下，胰腺癌细胞中HIF-3 α的表达比HIF-1 α和HIF-2 α的表达受到更大程度的刺激。胰腺癌组织中HIF-3 α蛋白水平也升高，与生存率降低、局部侵袭和远处转移增加有关，而在缺氧条件下，HIF-3 α的下调抑制了胰腺癌细胞的侵袭和迁移。在常氧条件下，HIF-3 α过表达促进胰腺癌细胞的侵袭和迁移，刺激f -肌动蛋白聚合。综上所述，HIF-3 α在体内促进胰腺癌细胞的侵袭和转移，通过转录激活RhoC-ROCK1信号通路促进胰腺癌细胞的侵袭和转移。(c) 2017 aacr。
Hypoxia contributes to pancreatic cancer progression and promotes its growth and invasion. Previous research principally focused on hypoxia-inducible factor-1 alpha (HIF-1 alpha) and HIF-2 alpha (HIF1A and EPAS1) as the major hypoxia-associated transcription factors in pancreatic cancer. However, the role of HIF-3 alpha (HIF3A) has not been investigated. Therefore, HIF-1 alpha, HIF-2 alpha, and HIF-3 alpha expression levels were measured under normoxic and hypoxic conditions. In addition, HIF-3 alpha expression was measured in human pancreatic cancer tissue specimens and the impact of altered HIF-3 alpha expression on cell invasion and migration was investigated in vitro and in vivo, as well as the underlying mechanisms. Under hypoxic conditions, HIF-3 alpha expression was stimulated in pancreatic cancer cells to a greater degree than HIF-1 alpha and HIF-2 alpha expression. HIF-3 alpha protein levels were also elevated in pancreatic cancer tissues and correlated with reduced survival and greater local invasion and distant metastasis, whereas knockdown of HIF-3 alpha, under hypoxic conditions, suppressed pancreatic cancer cell invasion and migration. Under normoxia, HIF-3 alpha overexpression promoted pancreatic cancer cell invasion and migration and stimulated F-actin polymerization. In summary, HIF-3 alpha promotes pancreatic cancer cell invasion and metastasis in vivo and promotes pancreatic cancer cell invasion and metastasis by transcriptionally activating the RhoC-ROCK1 signaling pathway. (C) 2017 AACR.