Caveolin-1 up-regulates CD 147 glycosylation and the invasive capability of murine hepatocarcinoma cell lines
Caveolin-1 up-regulates CD 147 glycosylation and the invasive capability of murine hepatocarcinoma cell lines
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DOI：
10.1016/j.biocel.2006.03.019
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发表时间：
2006-01-01
影响因子：
4
通讯作者：
Zhang, Jianing
中科院分区：
文献类型：
--
作者：
Jia, Li;Wang, Hujing;Zhang, Jianing
CD147是许多恶性肿瘤细胞表面基质金属蛋白酶（MMP）产生的调节因子，与Cav-1具有高度特异性的关联。由于不均匀的n -糖基化，CD147以高糖基化形式HG-CD147（类似于40-60kDa）和低糖基化形式lg -CD147（类似于32kDa）存在。本研究探讨了Cav-1在HcaF、HcaP和Hepa1-6小鼠肝癌细胞系（分别具有高、低和无淋巴结转移潜能）和正常小鼠肝细胞系IAR-20中CID 147糖基化的可能作用。采用RNA干扰（RNAi）策略，我们发现下调Hca-F/RNAi细胞中Cav-1的表达可以抑制LG-CD147向HG-CD147的转化，下调MMP-11的表达，减少Hca-F/RNAi细胞的侵袭。相反，在Hepal-6/Cav-1细胞中稳定高表达Cav-1可引起HG-CD147特异性升高，上调MMP-11蛋白表达，增强Hepal-6/Cav-1细胞侵袭。综上所述，Cav-1的表达导致HG-CD147相对于lg - cd147的比例增加，MMP-11的产生增加，侵袭能力增强。因此，Cav-1被认为既是致癌基因又是肿瘤抑制基因，可能是基因治疗的一个新的潜在靶点。(c) 2006 Elsevier Ltd.版权所有。
CD147 which is a regulator of matrix metalloproteinase (MMP) production on the surface of many malignant tumor cells, shows a highly specific association with caveolin-1 (Cav-1). As a result of heterogeneous N-glycosylation, CD147 exists in both highly glycosylated form, HG-CD147 (similar to 40-60kDa) and lowly glycosylated form, LG-CD 147 (similar to 32kDa). This study investigated the possible role of Cav-1 in CID 147 glycosylation in the HcaF, HcaP and Hepa1-6 mouse hepatocarcinoma cell lines, which have high, low and no metastatic potential in the lymph nodes, respectively, and in the normal mouse liver cell line IAR-20. Using an RNA interference (RNAi) strategy, we showed that the down-regulation of Cav-1 in Hca-F/RNAi cells could suppress the conversion of LG-CD147 to HG-CD147, down-regulate MMP-11 expression and decrease Hca-F/RNAi cell invasion. Conversely, a stable high expression of Cav-1 in Hepal-6/Cav-1 cell could cause a specific increase of HG-CD147, up-regulate MMP-11 protein expression and enhance Hepal-6/Cav-1 cell invasion. In conclusion, Cav-1 expression leads to an increased proportion of HG-CD147 relative to LG-CD 147, increased production of MMP-11 and a higher invasive capability. Cav-1 is therefore proposed to act as both an oncogene and a tumor suppressor gene, and could represent a new potential target for gene therapy. (c) 2006 Elsevier Ltd. All rights reserved.