Down-regulation of Gli-1 inhibits hepatocellular carcinoma cell migration and invasion
Down-regulation of Gli-1 inhibits hepatocellular carcinoma cell migration and invasion
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下调Gli-1抑制肝癌细胞迁移和侵袭
DOI：
10.1007/s11010-014-2071-x
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发表时间：
2014-08-01
影响因子：
4.3
通讯作者：
Huang, Xiao-Hui
中科院分区：
文献类型：
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作者：
Chen, Jing-Song;Li, Hua-Shu;Huang, Xiao-Hui
胶质瘤相关癌基因同源物-1（Gli-1）被认为是Hedgehog通路激活的标志物，与多种癌症的进展相关。我们以前曾报道Gli-1与肝细胞癌（HCC）的侵袭和转移相关。然而，Gli-1在HCC侵袭中的确切作用和机制尚不清楚。在这项研究中，我们发现，小干扰RNA介导的下调Gli-1的表达显着抑制SMMC-7721和SK-Hep 1细胞的粘附，运动，迁移和侵袭。此外，下调Gli-1显著降低基质金属蛋白酶（MMP）-2和MMP-9的表达和活性。此外，我们发现Gli-1的下调导致E-cadherin的上调以及伴随的Snail和Vimentin的下调，这与上皮-间质转化（EMT）的抑制一致。综上所述，我们的研究结果表明，下调Gli-1可能通过抑制MMP-2，9的表达和激活以及阻断EMT来抑制HCC细胞的迁移和侵袭。
Glioma-associated oncogene homolog-1 (Gli-1) is considered a marker of Hedgehog pathway activation and is associated with the progression of several cancers. We have previously reported that Gli-1 was correlated with invasion and metastasis in hepatocellular carcinoma (HCC). However, the exact roles and mechanisms of Gli-1 in HCC invasion are unclear. In this study, we found that small interfering RNA mediated down-regulation of Gli-1 expression significantly suppressed adhesion, motility, migration, and invasion of both SMMC-7721 and SK-Hep1 cells. Furthermore, down-regulation of Gli-1 significantly reduced expressions and activities of both matrix metalloproteinase (MMP)-2 and MMP-9. In addition, we found that down-regulation of Gli-1 resulted in up-regulation of E-cadherin and concomitant down-regulation of Snail and Vimentin, consistent with inhibition of epithelial-mesenchymal transition (EMT). Taken together, our results suggest that down-regulation of Gli-1 suppresses HCC cell migration and invasion likely through inhibiting expressions and activations of MMP-2, 9 and blocking EMT.