HER2-mediated upregulation of MMP-1 is involved in gastric cancer cell invasion
HER2-mediated upregulation of MMP-1 is involved in gastric cancer cell invasion
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DOI：
10.1016/j.abb.2010.05.009
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发表时间：
2010-07-01
影响因子：
3.9
通讯作者：
Yang, An-Gang
中科院分区：
文献类型：
--
作者：
Bao, Wei;Fu, Hai-Jing;Yang, An-Gang
HER 2过表达与转移有关，转移是胃癌患者死亡的主要原因。在这项研究中，我们证明了基于载体的shRNA显着敲低HER 2的表达，并显着抑制胃癌细胞的迁移和侵袭。HER 2敲低导致MMP-1的表达下调，而HER 2过表达通过激活MMP-1启动子而提高MMP-1的转录。发现MMP-1的启动子区在约2500和约2000 bp之间对于上调HER 2介导的转录至关重要。此外，截短的启动子（-70至+63）不显示任何转录活性。当MMP-1被敲低时，细胞侵袭活性几乎被完全抑制。相反，MMP-1的过表达部分地挽救了具有敲低的HER 2的细胞株的侵袭能力。这些发现有助于进一步了解HER 2促进恶性肿瘤的分子机制，并表明在胃癌治疗中可能需要靶向HER 2和MMP-1以有效阻断HER 2信号传导。(c)2010年爱思唯尔公司All rights reserved.
HER2 overexpression is associated with metastasis the main cause of death in individuals with gastric cancer. In this study, we demonstrated that vector-based shRNA significantly knocked down the expression of HER2 and considerably inhibited both the migration and invasion of gastric cancer cells. HER2 knockdown resulted in the downregulation of the expression of MMP-1, while HER2 overexpression improved the transcription of MMP-1 through the activation of an MMP-1 promoter. The promoter region of MMP-1 between -2500 and -2000 bp was found to be crucial for the upregulation of HER2-mediated transcription. Furthermore, a truncated promoter (-70 to + 63) did not display any transcriptional activity. Cell invasion activity was almost completely inhibited when MMP-1 was knocked down. Conversely, the overexpression of MMP-1 partly rescued the invasion ability of cell strains with knocked-down HER2. These findings help further understanding of the molecular mechanisms through which HER2 promotes malignancy, and suggest that targeting both HER2 and MMP-1 may be required to effectively block HER2 signaling in gastric cancer therapy. (c) 2010 Elsevier Inc. All rights reserved.