HER2-mediated upregulation of MMP-1 is involved in gastric cancer cell invasion
- PMID: 20460098
- DOI: 10.1016/j.abb.2010.05.009
HER2-mediated upregulation of MMP-1 is involved in gastric cancer cell invasion
Abstract
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.
Copyright 2010 Elsevier Inc. All rights reserved.
Similar articles
-
MMP-9 is increased in the pathogenesis of gastric cancer by the mediation of HER2.Cancer Gene Ther. 2015 Apr;22(3):101-7. doi: 10.1038/cgt.2014.61. Epub 2015 Jan 30. Cancer Gene Ther. 2015. PMID: 25633484
-
Gonadotropin-releasing hormone promotes ovarian cancer cell invasiveness through c-Jun NH2-terminal kinase-mediated activation of matrix metalloproteinase (MMP)-2 and MMP-9.Cancer Res. 2006 Nov 15;66(22):10902-10. doi: 10.1158/0008-5472.CAN-06-2217. Cancer Res. 2006. PMID: 17108127
-
Sonic hedgehog signaling promotes motility and invasiveness of gastric cancer cells through TGF-beta-mediated activation of the ALK5-Smad 3 pathway.Carcinogenesis. 2008 Mar;29(3):480-90. doi: 10.1093/carcin/bgm281. Epub 2008 Jan 3. Carcinogenesis. 2008. PMID: 18174246
-
CNK1 promotes invasion of cancer cells through NF-kappaB-dependent signaling.Mol Cancer Res. 2010 Mar;8(3):395-406. doi: 10.1158/1541-7786.MCR-09-0296. Epub 2010 Mar 2. Mol Cancer Res. 2010. PMID: 20197385
-
Role of matrix metalloproteinase-2 in ethanol-induced invasion by breast cancer cells.J Gastroenterol Hepatol. 2006 Oct;21 Suppl 3:S65-8. doi: 10.1111/j.1440-1746.2006.04578.x. J Gastroenterol Hepatol. 2006. PMID: 16958676 Review.
Cited by
-
Effect of androgen blockade on HER-2 and matrix metalloproteinase-2 expression on bone marrow micrometastasis and stromal cells in men with prostate cancer.ScientificWorldJournal. 2013 May 14;2013:281291. doi: 10.1155/2013/281291. Print 2013. ScientificWorldJournal. 2013. PMID: 23766685 Free PMC article. Clinical Trial.
-
Morbid Obesity in Women Is Associated with an Altered Intestinal Expression of Genes Related to Cancer Risk and Immune, Defensive, and Antimicrobial Response.Biomedicines. 2022 Apr 29;10(5):1024. doi: 10.3390/biomedicines10051024. Biomedicines. 2022. PMID: 35625760 Free PMC article.
-
Exploration of an Prognostic Signature Related to Endoplasmic Reticulum Stress in Colorectal Adenocarcinoma and Their Response Targeting Immunotherapy.Technol Cancer Res Treat. 2023 Jan-Dec;22:15330338231212073. doi: 10.1177/15330338231212073. Technol Cancer Res Treat. 2023. PMID: 37920989 Free PMC article.
-
Matrix metalloproteinase-driven epithelial-mesenchymal transition: implications in health and disease.J Transl Med. 2025 Apr 11;23(1):436. doi: 10.1186/s12967-025-06447-w. J Transl Med. 2025. PMID: 40217300 Free PMC article. Review.
-
Identification of Potential Key Genes Associated With the Pathogenesis and Prognosis of Gastric Cancer Based on Integrated Bioinformatics Analysis.Front Genet. 2018 Jul 17;9:265. doi: 10.3389/fgene.2018.00265. eCollection 2018. Front Genet. 2018. PMID: 30065754 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
Miscellaneous