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Molecular Signature of MT1-MMP: Transactivation of the Downstream Universal Gene in Cancer

ABSTRACT: Genome-wide expression profiling of MT1-MMP–overexpressing versus MT1-MMP–silenced cancer cells and a further data mining analysis of the preexisting expression database of 190 human tumors of 14 cancer types led us to identify 11 genes, the expression of which correlated firmly and universally with that of MT1-MMP (P < 0.00001).

ORGANISM(S): Homo sapiens

PROVIDER: GSE11668 | GEO | 2008/06/11

SECONDARY ACCESSION(S): PRJNA106065

REPOSITORIES: GEO

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MT1-MMP induces malignant transformation in Mammary cells

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Inhibition of ß1 integrin induces its association with MT1-MMP and decreases MT1- MMP internalization and cellular invasiveness

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2022-12-22 | PXD024000 | Pride

Expression array of early postnatal Mt1-mmp-targeted mammary glands

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RNAi profiling of human fibrosarcoma cell line knocked down for MT1-MMP

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Extracellular Matrix Proteolysis by MT1-MMP is Associated with Influenza-Related Mortality

Project description:The balance between protecting tissue integrity and efficient immune response is critical for host survival. Here we investigate the role of extracellular matrix (ECM) proteolysis in achieving this balance in the lung during influenza virus infection using a combined genomic and proteomic approach. We followed the transcriptional dynamics and ECM- related responses in a mouse model of influenza virus infection, integrated with whole tissue imaging and functional assays. Our study identifies MT1-MMP as a prominent host-ECM-remodeling collagenase in influenza virus infection. We show that selective inhibition of MT1-MMP-driven ECM proteolysis protects the tissue from infection-related structural and compositional damage. Inhibition of MT1-MMP did not significantly alter the immune response or cytokine expression, indicating its dominant role in ECM remodeling. We demonstrate that the available treatment for influenza virus (Tamiflu/ Oseltamivir) does not prevent lung ECM damage and is less effective than anti-MT1-MMP treatment in influenza virus and Streptococcus pneumoniae coinfection paradigms. Importantly, combination therapy of Tamiflu with anti-MT1-MMP shows a strong synergistic effect and results in complete recovery in mice. This study highlights the importance of tissue tolerance agents for surviving infectious diseases, and the potential of such host-pathogen therapy combination for respiratory infections.

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