血管生成拟态
生物
癌症研究
上皮-间质转换
肝细胞癌
血管生成
热休克蛋白90
MMP2型
转移
癌症
热休克蛋白
生物化学
遗传学
基因
作者
Jing Meng,Shuang Chen,Yue-Yang Lei,Jing Han,Weilong Zhong,Xiaorui Wang,Yanrong Liu,Wan-Feng Gao,Qiang Zhang,Qiang Tan,Huijuan Liu,Honggang Zhou,Tao Sun,Cheng Yang
出处
期刊:Oncogene
[Springer Nature]
日期:2018-08-07
卷期号:38 (2): 228-243
被引量:56
标识
DOI:10.1038/s41388-018-0428-4
摘要
Hepatocellular carcinoma (HCC) is a typical hypervascular solid tumor. Vasculogenic mimicry (VM) formed by aggressive tumor cells to mimic vasculogenic networks plays an important role in the tumor malignancy of HCC. Hsp90β promotes endothelial cell-dependent angiogenesis in HCC. However, the relationship between Hsp90β and VM formation is unclear. In this study, we found that Hsp90β is positively correlated with VM and EMT marker proteins in HCC tissues and promotes tube formation, cell migration, and invasion in vitro. Hsp90β interacts with Twist1 and promotes its deubiquitination and stabilization to nuclear translocation and enhances the VE-cadherin promoter activity. Results of in vitro analysis indicate that Hsp90β enhances the tumor VM in tumor-burdened mice, and the Hsp90 inhibitor NVP-BEP800 suppresses VM formation by releasing Hsp90β and Twist1 interaction. This study provides a potential antitumor therapy for inhibiting VM by targeting Hsp90β in HCC.
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