Searching across hundreds of databases
Matrix metalloproteinases (MMPs) degrade and modify the extracellular matrix (ECM) as well as cell-ECM and cell-cell contacts, facilitating detachment of epithelial cells from the surrounding tissue. MMPs play key functions in embryonic development and mammary gland branching morphogenesis, but they are also upregulated in breast cancer, where they stimulate tumorigenesis, cancer cell invasion and metastasis. MMPs have been investigated as potential targets for cancer therapy, but clinical trials using broad-spectrum MMP inhibitors yielded disappointing results, due in part to lack of specificity toward individual MMPs and specific stages of tumor development. Epithelial-mesenchymal transition (EMT) is a developmental process in which epithelial cells take on the characteristics of invasive mesenchymal cells, and activation of EMT has been implicated in tumor progression. Recent findings have implicated MMPs as promoters and mediators of developmental and pathogenic EMT processes in the breast. In this review, we will summarize recent studies showing how MMPs activate EMT in mammary gland development and in breast cancer, and how MMPs mediate breast cancer cell motility, invasion, and EMT-driven breast cancer progression. We also suggest approaches to inhibit these MMP-mediated malignant processes for therapeutic benefit.
Pubmed ID: 20440544 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
A database of human, chimpanzee, mouse, and rat proteases and protease inhibitors, as well as as the growing number of hereditary diseases caused by mutations in protease genes. Analysis of the human and mouse genomes has allowed us to annotate 581 human, 580 chimpanzee, 667 mouse, and 655 rat protease genes. Proteases are classified in five different classes according to their mechanism of catalysis. Proteases are a diverse and important group of enzymes representing >2% of the human, chimpanzee, mouse and rat genomes. This group of enzymes is implicated in numerous physiological processes. The importance of proteases is illustrated by the existence of 99 different hereditary diseases due to mutations in protease genes. Furthermore, proteases have been implicated in multiple human pathologies, including vascular diseases, rheumatoid arthritis, neurodegenerative processes, and cancer. During the last ten years, our laboratory has identified and characterized more than 60 human protease genes. Due to the importance of proteolytic enzymes in human physiology and pathology, we have recently introduced the concept of Degradome, as the complete repertoire of proteases expressed by a tissue or organism. Thanks to the recent completion of the human, chimpanzee, mouse, and rat genome sequencing projects, we were able to analyze and compare for the first time the complete protease repertoire in those mammalian organisms, as well as the complement of protease inhibitor genes. This webpage also contains the Supplementary Material of Human and mouse proteases: a comparative genomic approach Nat Rev Genet (2003) 4: 544-558, Genome sequence of the brown Norway rat yields insights into mammalian evolution Nature (2004) 428: 493-521, A genomic analysis of rat proteases and protease inhibitors Genome Res. (2004) 14: 609-622, and Comparative genomic analysis of human and chimpanzee proteases Genomics (2005) 86: 638-647.
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
scicrunch.org
