HIF-1α Plays a Role in the Chemotactic Migration of Hepatocarcinoma Cells Through the Modulation of CXCL6 Expression
HIF-1α Plays a Role in the Chemotactic Migration of Hepatocarcinoma Cells Through the Modulation of CXCL6 Expression
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DOI：
10.1159/000366357
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发表时间：
2014-01-01
影响因子：
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通讯作者：
Xia, Jinglin
中科院分区：
文献类型：
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作者：
Tian, Hui;Huang, Peixin;Xia, Jinglin
背景/目的：缺氧促进肝细胞癌（HCC）的进展和转移。缺氧诱导因子-α (HIF-1 α) 调节参与肿瘤生长、血管生成和转移的各种趋化因子的表达。方法：在细胞系和患者样本中研究 HIF-1 α 在 HCC 肿瘤生长和侵袭以及 HCC 患者预后中的作用。通过 qRT-PCR 和蛋白质印迹评估 HIF-1 α mRNA 和蛋白质水平。沉默 HIF-1 α 会下调 HCC 细胞中粒细胞趋化蛋白 2 (GCP-2)/CXCL6（一种 CXC ELR+ 趋化因子）的表达，荧光素酶测定显示 HIF-1 α 与 CXCL6 启动子中的缺氧反应元件结合并调节其转录。缺氧诱导的 HIF-1 α 促进了体外 HCC 细胞的迁移和侵袭，而这种作用被抗 CXCL6 抗体抑制。结果：HIF-1α 在 HCC 细胞系和组织中表达上调，其促进侵袭和转移的作用是通过其与促血管生成趋化因子 CXCL6 的直接相互作用介导的。 CXCL6表达与HCC患者的不良预后相关。结论：HIF-1α通过上调HCC细胞CXCL6转录促进HCC进展和转移，为HCC的治疗提供潜在的新靶点。版权所有 (C) 2014 S. Karger AG，巴塞尔
Background/Aims: Hypoxia promotes the progression and metastasis of hepatocellular carcinoma (HCC). Hypoxia inducible factor-alpha (HIF-1 alpha) regulates the expression of various chemokines involved in tumor growth, angiogenesis and metastasis. Methods: The role of HIF-1 alpha in HCC tumor growth and invasion and the prognosis of patients with HCC was investigated in cell lines and patient samples. HIF-1 alpha mRNA and protein levels were assessed by qRT-PCR and western blotting. Silencing of HIF-1 alpha downregulated the expression of granulocyte chemotactic protein-2 (GCP-2)/CXCL6, a CXC ELR+ chemokine, in HCC cells, and a luciferase assay showed that HIF-1 alpha binds to a hypoxia response element in the promoter of CXCL6 and regulates its transcription. Induction of HIF-1 alpha by hypoxia promoted the migration and invasion of HCC cells in vitro, and this effect was suppressed by an anti-CXCL6 antibody. Results: HIF-1 alpha is upregulated in HCC cell lines and tissues and its effect on promoting invasion and metastasis is mediated by its direct interaction with the pro-angiogenic chemokine CXCL6. CXCL6 expression was associated with poor prognosis of HCC patients. Conclusion: HIF-1 alpha promotes HCC progression and metastasis by upregulating CXCL6 transcription in HCC cells, providing a potential novel therapeutic target for the treatment of HCC. Copyright (C) 2014 S. Karger AG, Basel