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.

中文翻译：

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Hsp90β 通过肝细胞癌中的上皮-间质转化促进侵袭性血管生成拟态。

肝细胞癌（HCC）是一种典型的富血管实体瘤。由侵袭性肿瘤细胞形成的模拟血管生成网络的血管生成拟态（VM）在 HCC 肿瘤恶性肿瘤中发挥着重要作用。Hsp90β 促进 HCC 中内皮细胞依赖性血管生成。然而，Hsp90β与VM形成之间的关系尚不清楚。在本研究中，我们发现Hsp90β与HCC组织中的VM和EMT标志蛋白呈正相关，并在体外促进管形成、细胞迁移和侵袭。Hsp90β 与 Twist1 相互作用，促进其去泛素化和核转位稳定，并增强 VE-钙粘蛋白启动子活性。体外分析结果表明，Hsp90β 可增强荷瘤小鼠的肿瘤 VM，而 Hsp90 抑制剂 NVP-BEP800 通过释放 Hsp90β 与 Twist1 的相互作用来抑制 VM 形成。这项研究提供了一种潜在的抗肿瘤疗法，通过靶向 HCC 中的 Hsp90β 来抑制 VM。