Increased expression of S100A6 promotes cell proliferation and migration in human hepatocellular carcinoma
Increased expression of S100A6 promotes cell proliferation and migration in human hepatocellular carcinoma
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S100A6表达增加促进人肝细胞癌细胞增殖和迁移
DOI：
10.1007/s00109-013-1104-3
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发表时间：
2014-03-01
影响因子：
4.7
通讯作者：
Wei, Yuquan
中科院分区：
文献类型：
--
作者：
Li, Ziqiang;Tang, Mei;Wei, Yuquan
高水平的S100 A6与某些类型的人类癌症的预后不良有关，但S100 A6在这些癌症的分子发病机制中的作用在很大程度上是未知的。本研究旨在探讨S100 A6在肝细胞癌（HCC）中的表达及其功能。采用免疫组化方法检测S100 A6在肝癌组织及癌旁组织中的表达。通过人肝癌细胞的增殖、迁移和侵袭实验，分析了S100 A6在肿瘤发生和转移中的潜在功能。此外，通过表达和纯化的S100 A6重组蛋白标记的细胞穿透肽，我们分析了其复杂的细胞外/细胞内的影响在S100 A6沉默的细胞模型。因此，S100 A6在人HCC中的表达与癌旁组织相比上调。S100 A6沉默抑制肝癌细胞的生长和运动，而S100 A6的细胞内重新表达可以挽救增殖和迁移缺陷。S100 A6的细胞内过表达导致E-cadherin表达下调，并促进β-catenin的核积聚。此外，我们发现S100 A6刺激后细胞增殖和运动的增强依赖于PI 3 K/ AKT通路的激活。这些结果提示S100 A6可能参与了人肝癌的促进和发展。
High levels of S100A6 have been associated with poor outcome in some types of human cancers, but the role of S100A6 in the molecular pathogenesis of these cancers is largely unknown. This study was performed to explore the expression and functional roles of S100A6 in hepatocellular carcinoma (HCC). The expression level of S100A6 in HCC tumor and corresponding peritumoral tissues were determined by immunohistochemistry analysis. The potential functions of S100A6 in tumorigenesis and metastasis were analyzed by cell proliferation, migration, and invasion assays in human liver cancer cells. Moreover, through expression and purification of S100A6 recombinant protein tagged with cell-penetrating peptide, we analyzed its complex extracellular/intracellular effects in a S100A6-silenced cellular model. As a result, the expression of S100A6 was up-regulated in human HCC compared with adjacent peritumoral tissues. S100A6 silencing inhibited the growth and motility of HCC cells, while intracellular re-expression of S100A6 could rescue the proliferation and migration defects. Intracellular overexpression of S100A6 resulted in down-regulation of E-cadherin expression and promoted nuclear accumulation of beta-catenin. Moreover, we found that the enhanced cell proliferation and motility after S100A6 stimulation were dependent on the activation of PI3K/ AKT pathway. These results suggest that S100A6 may be involved in promotion and progression of human liver cancer.