Gai Xiaohong, Lu Zhongtang, Tu Kangsheng, Liang Zheyong, Zheng Xin
Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
PLoS One. 2014 Jan 13;9(1):e84551. doi: 10.1371/journal.pone.0084551. eCollection 2014.
Caveolin-1 (Cav-1) has been recently identified to be over-expressed in hepatocellular carcinoma (HCC) and promote HCC cell motility and invasion ability via inducing epithelial-mesenchymal transition (EMT). However, the mechanism of aberrant overexpression of Cav-1 remains vague. Here, we observed that Cav-1 expression was positively associated with GLI1 expression in HCC tissues. Forced expression of GLI1 up-regulated Cav-1 in Huh7 cells, while knockdown of GLI1 decreased expression of Cav-1 in SNU449 cells. Additionally, silencing Cav-1 abolished GLI1-induced EMT of Huh7 cells. The correlation between GLI1 and Cav-1 was confirmed in tumor specimens from HCC patients and Cav-1 was found to be associated with poor prognosis after hepatic resection. The relationship between protein expression of GLI1 and Cav-1 was also established in HCC xenografts of nude mice. These results suggest that GLI1 may be attributed to Cav-1 up-regulation which plays an important role in GLI1-driven EMT phenotype in HCC.
小窝蛋白-1（Cav-1）最近被发现于肝细胞癌（HCC）中过度表达，并通过诱导上皮-间质转化（EMT）促进肝癌细胞的运动性和侵袭能力。然而，Cav-1异常过表达的机制仍不明确。在此，我们观察到在肝癌组织中Cav-1表达与GLI1表达呈正相关。在Huh7细胞中强制表达GLI1可上调Cav-1，而在SNU449细胞中敲低GLI1则降低Cav-1的表达。此外，沉默Cav-1可消除GLI1诱导的Huh7细胞EMT。在肝癌患者的肿瘤标本中证实了GLI1与Cav-1之间的相关性，并且发现Cav-1与肝切除术后的不良预后相关。在裸鼠的肝癌异种移植模型中也建立了GLI1和Cav-1蛋白表达之间的关系。这些结果表明，GLI1可能导致Cav-1上调，而Cav-1在GLI1驱动的肝癌EMT表型中起重要作用。
