Ru Ning-Yu, Wu Jiao, Chen Zhi-Nan, Bian Huijie
Cell Engineering Research Center and Department of Cell Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an, 710032, China; Department of Aerospace Physiology, Fourth Military Medical University, Xi'an, 710032, China.
Cell Biol Int. 2015 Jan;39(1):44-51. doi: 10.1002/cbin.10341. Epub 2014 Aug 11.
Epithelial-mesenchymal transition (EMT) induced by the transforming growth factor beta (TGF-β) is involved in hepatocarcinogenesis and hepatocellular carcinoma (HCC) metastasis. HAb18G/CD147, a member of the immunoglobulin family, plays an important role in tumor invasion and metastasis. HAb18G/CD147 promotes EMT of hepatocytes through TGF-β signaling and is transcriptionally regulated by Slug. We investigated the role of HAb18G/CD147 in TGF-β-induced EMT in HCC invasion. Two human HCC cell lines, SMMC-7721 and HepG2, were used to determine the role of HAb18G/CD147 in EMT. Upregulation of HAb18G/CD147 induced by the high doses of TGF-β1 in SMMC-7721 (5 ng/mL) and HepG2 cells (10 ng/mL) (P < 0.05). CD147 upregulation was coupled with upregulation of Snail1 and Slug. CD147 knockout significantly decreased the expression of N-cadherin and vimentin, and colony formation ability of SMMC-7721 cells. TGF-β1 enhanced the migration capacity of SMMC-7721 cells, which was markedly attenuated by CD147 knockdown. Thus, HAb18G/CD147 is involved in TGF-β-induced EMT and HCC invasion.
转化生长因子β（TGF-β）诱导的上皮-间质转化（EMT）参与肝癌发生及肝细胞癌（HCC）转移。免疫球蛋白家族成员HAb18G/CD147在肿瘤侵袭和转移中起重要作用。HAb18G/CD147通过TGF-β信号通路促进肝细胞的EMT，并受Slug转录调控。我们研究了HAb18G/CD147在TGF-β诱导的EMT促进HCC侵袭中的作用。使用两种人HCC细胞系SMMC-7721和HepG2来确定HAb18G/CD147在EMT中的作用。高剂量TGF-β1（SMMC-7721细胞为5 ng/mL，HepG2细胞为10 ng/mL）可诱导SMMC-7721和HepG2细胞中HAb18G/CD147表达上调（P < 0.05）。CD147上调与Snail1和Slug上调相关。CD147基因敲除显著降低SMMC-7721细胞中N-钙黏蛋白和波形蛋白的表达以及集落形成能力。TGF-β1增强SMMC-7721细胞的迁移能力，而CD147敲低可显著减弱这种能力。因此，HAb18G/CD147参与TGF-β诱导的EMT及HCC侵袭。
