Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China; Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
Exp Cell Res. 2019 Aug 1;381(1):66-76. doi: 10.1016/j.yexcr.2019.04.030. Epub 2019 Apr 30.
The expression of HS-1-associated protein X-1 (HAX-1) plays a major role in the development of hepatocellular carcinoma (HCC). However, the function of HAX-1 in HCC metastasis is unclear. Quantitative real-time PCR and western blotting were used to examine HAX-1 expression in HCC cell lines with different metastatic potential, and in tumor tissues with or without intrahepatic metastasis. HCC tissue arrays (n = 144) were used to assess correlations between clinicopathological parameters and HAX-1 expression. We also examined the effect of HAX-1 on promoting HCC cell metastasis in vivo and in vitro. The results showed that the expression levels of HAX-1 were higher in metastatic HCC cell lines than in non-metastatic HCC cell lines. HAX-1 was also significantly upregulated in primary HCC tissues with intrahepatic metastasis compared with those without intrahepatic metastasis. HCC in patients with high HAX-1 expression is more likely to metastasize. HAX-1 expression was associated with malignant progression and poor prognosis, and HAX1 silencing inhibited HCC cell migration and invasion in vitro and decreased HCC cell lung metastasis in vivo, whereas HAX-1 overexpression had the inverse effect. Moreover, HAX-1 increased HCC cell metastasis by promoting the epithelial-mesenchymal transition (EMT) process. Finally, we revealed that HAX-1 modulated EMT in HCC cells by increasing NF-κB/p65 nuclear translocation. In conclusion, HAX-1 promotes HCC metastasis by EMT through activating the NF-κB pathway, suggesting that HAX-1 could be a potential therapeutic target for HCC treatment.
HS-1 相关蛋白 X-1（HAX-1）的表达在肝细胞癌（HCC）的发展中起着重要作用。然而，HAX-1 在 HCC 转移中的功能尚不清楚。我们使用定量实时 PCR 和 Western blot 检测了具有不同转移潜能的 HCC 细胞系以及有或无肝内转移的肿瘤组织中 HAX-1 的表达。我们还使用 HCC 组织芯片（n=144）评估了 HAX-1 表达与临床病理参数之间的相关性。我们还研究了 HAX-1 对促进 HCC 细胞转移的体内和体外的影响。结果表明，转移性 HCC 细胞系中的 HAX-1 表达水平高于非转移性 HCC 细胞系。与无肝内转移的 HCC 组织相比，具有肝内转移的原发性 HCC 组织中 HAX-1 的表达显著上调。HAX-1 高表达的 HCC 更易发生转移。HAX-1 表达与恶性进展和预后不良相关，沉默 HAX1 可抑制 HCC 细胞的迁移和侵袭，并减少 HCC 细胞在体内的肺转移，而 HAX-1 过表达则具有相反的效果。此外，HAX-1 通过促进上皮-间充质转化（EMT）过程增加 HCC 细胞的转移。最后，我们揭示了 HAX-1 通过增加 NF-κB/p65 核易位来调节 HCC 细胞中的 EMT。总之，HAX-1 通过 EMT 促进 HCC 转移，通过激活 NF-κB 通路，提示 HAX-1 可能成为 HCC 治疗的潜在治疗靶点。
