HGF 通过 hBVR 通路诱导非小细胞肺癌 EMT。
HGF induces EMT in non-small-cell lung cancer through the hBVR pathway.
机构信息
Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Harbin 150081, China; Key Laboratory of Pulmonary Circulatory System Diseases of Heilongjiang Academy of Medical Sciences, Harbin 150081, China; State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin 150081, China.
Key Laboratory of Pulmonary Circulatory System Diseases of Heilongjiang Academy of Medical Sciences, Harbin 150081, China; Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin 150081, China; State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin 150081, China; Central Laboratory of Harbin Medical University-Daqing, Daqing 163319, China.
出版信息
Eur J Pharmacol. 2017 Sep 15;811:180-190. doi: 10.1016/j.ejphar.2017.05.040. Epub 2017 May 26.
The epithelial-to-mesenchymal transition (EMT) is a crucial event during non-small-cell lung cancer (NSCLC) invasion and metastasis. However, the mechanisms involved in NSCLC EMT have not been fully clarified. Hepatocyte growth factor (HGF) and human biliverdin reductase (hBVR) are reported to contribute to EMT in several diseases. Here, we show that compared with transforming growth factor beta (TGF-β), fibroblast growth factor (FGF), and epidermal growth factor (EGF), HGF is an important cell factor for EMT in NSCLC cell lines A549 and H460. Met protein, HGF receptors, and hBVR were found to be highly expressed and positively correlated with EMT in NSCLC tissue sections. In addition, HGF and hBVR induced a decrease in epithelial protein marker expression and an increase in mesenchymal protein marker expression as well as increased cellular migration and invasion, indicating that both HGF and hBVR mediate EMT in A549 and H460 cell lines. Furthermore, HGF-induced EMT and migration and invasion in both cell lines was inhibited by si-hBVR. Taken together, our data show that HGF induces EMT in NSCLC through the hBVR pathway.
上皮-间充质转化（EMT）是非小细胞肺癌（NSCLC）侵袭和转移过程中的一个关键事件。然而，NSCLC EMT 涉及的机制尚未完全阐明。肝细胞生长因子（HGF）和人胆红素还原酶（hBVR）在几种疾病中被报道有助于 EMT。在这里，我们表明与转化生长因子-β（TGF-β）、成纤维细胞生长因子（FGF）和表皮生长因子（EGF）相比，HGF 是 NSCLC 细胞系 A549 和 H460 中 EMT 的重要细胞因子。在 NSCLC 组织切片中发现 Met 蛋白、HGF 受体和 hBVR 高度表达且与 EMT 呈正相关。此外，HGF 和 hBVR 诱导上皮蛋白标志物表达减少和间充质蛋白标志物表达增加以及细胞迁移和侵袭增加，表明 HGF 和 hBVR 均可介导 A549 和 H460 细胞系中的 EMT。此外，si-hBVR 抑制了 HGF 诱导的这两种细胞系中的 EMT、迁移和侵袭。综上所述，我们的数据表明 HGF 通过 hBVR 途径诱导 NSCLC 中的 EMT。
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