PDF(Pubmed)
Abstract：
Metastasis is a major obstacle in the treatment of hepatocellular carcinoma (HCC). Microtubule-associated protein 4 (MAP4) plays an important role as a coordinator between microtubules and microfilaments. However, the role of MAP4 in HCC migration and epithelial mesenchymal transition (EMT) is unclear. We compared the protein and mRNA levels of MAP4 in human HCC and adjacent normal tissues using western blotting, immunohistochemistry and RT-qPCR. The migration and invasion abilities and the levels of EMT markers (E-Cadherin, N-Cadherin, Vimentin, and Snail) were compared between MAP4-knockdown and MAP4-overexpressed HCC cells. Finally, we examined whether β-catenin and glycogen synthase kinase 3β (GSK3β) are involved in the stimulatory effects of MAP4 on HCC migration, invasion and EMT. The results revealed that MAP4 levels were higher in the HCC tissues than in the normal hepatic tissues. More importantly, MAP4 knockdown suppressed migration and invasion abilities and EMT processes in HCC cells, which were confirmed by the stimulatory effects of MAP4 overexpression on EMT processes in HCC cells. Further evidence demonstrated that the up-regulation of β-catenin activity induced by the interaction between MAP4 and GSK3β possibly accounted for the pro-migration and pro-EMT effects of MAP4 on HCC cells. Taken together, these results suggest that MAP4 promotes migration, invasion, and EMT in HCC cells by regulating the GSK3β/β-catenin pathway.
摘要：
转移是肝细胞癌（HCC）治疗的主要障碍。微管相关蛋白4（MAP4）作为微管和微丝之间的协调器发挥着重要作用。然而,MAP4在HCC迁移和上皮间质转化（EMT）中的作用尚不清楚。我们使用蛋白质印迹法比较了人肝癌和邻近正常组织中MAP4的蛋白质和mRNA水平，免疫组织化学和RT-qPCR。迁移和入侵能力以及EMT标记水平(E-Cadherin，N-钙黏着蛋白,Vimentin,和Snail）在MAP4敲低和MAP4过表达的HCC细胞之间进行比较。最后,我们检查了β-连环蛋白和糖原合成酶激酶3β（GSK3β）是否参与MAP4对HCC迁移的刺激作用，入侵和EMT。结果显示，HCC组织中的MAP4水平高于正常肝组织。更重要的是,MAP4敲低抑制HCC细胞的迁移和侵袭能力以及EMT过程，MAP4过表达对HCC细胞EMT过程的刺激作用证实了这一点。进一步的证据表明，由MAP4和GSK3β之间的相互作用引起的β-catenin活性的上调可能是MAP4对HCC细胞的促迁移和促EMT作用的原因。一起来看,这些结果表明，MAP4促进迁移，入侵,并通过调节GSK3β/β-catenin通路在HCC细胞中进行EMT。
