Integrated multi-omics investigations of metalloproteinases in colon cancer: Focus on MMP2 and MMP9
Autor: | Ida Pucci-Minafra, Gianluca Di Cara, Salvatore Feo, Patrizia Cancemi, Miriam Buttacavoli, Elena Roz |
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Přispěvatelé: | Buttacavoli M., Di Cara G., Roz E., Pucci-Minafra I., Feo S., Cancemi P. |
Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Proteomics
MMP2 Epithelial-Mesenchymal Transition QH301-705.5 Colorectal cancer Bioinformatics Kaplan-Meier Estimate Biology Matrix metalloproteinase MMP9 Article Catalysis Epigenesis Genetic Metastasis Cohort Studies Inorganic Chemistry Lymphocytes Tumor-Infiltrating medicine Humans Epithelial–mesenchymal transition Biology (General) Physical and Theoretical Chemistry Settore BIO/06 - Anatomia Comparata E Citologia QD1-999 Molecular Biology Spectroscopy Tissue Inhibitor of Metalloproteinase-2 Functional analysis Organic Chemistry Proteolytic enzymes General Medicine medicine.disease Prognosis Computer Science Applications Colon cancer Extracellular Matrix Gene Expression Regulation Neoplastic Chemistry Matrix metalloproteinases Matrix Metalloproteinase 9 Tumor progression Case-Control Studies Colonic Neoplasms Cancer research Matrix Metalloproteinase 2 Gene expression |
Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 22 International Journal of Molecular Sciences, Vol 22, Iss 12389, p 12389 (2021) |
Popis: | Colorectal cancer (CRC) develops by genetic and epigenetic alterations. However, the molecular mechanisms underlying metastatic dissemination remain unclear and could benefit from multi-omics investigations of specific protein families. Matrix metalloproteinases (MMPs) are proteolytic enzymes involved in ECM remodeling and the processing of bioactive molecules. Increased MMP expression promotes the hallmarks of tumor progression, including angiogenesis, invasion, and metastasis, and is correlated with a shortened survival. Nevertheless, the collective role and the possible coordination of MMP members in CRC are poorly investigated. Here, we performed a multi-omics analysis of MMP expression in CRC using data mining and experimental investigations. Several databases were used to deeply mine different expressions between tumor and normal tissues, the genetic and epigenetic alterations, the prognostic value as well as the interrelationships with tumor immune-infiltrating cells (TIICs). A special focus was placed on to MMP2 and MMP9: their expression was correlated with immune markers and the interaction network of co-expressed genes disclosed their implication in epithelial to mesenchymal transition (EMT) and immune response. Finally, the activity levels of MMP2 and MMP9 in a cohort of colon cancer samples, including tissues and the corresponding sera, was also investigated by zymography. Our findings suggested that MMPs could have a high potency, as they are targeted in colon cancer, and might serve as novel biomarkers, especially for their involvement in the immune response. However, further studies are needed to explore the detailed biological functions and molecular mechanisms of MMPs in CRC, also in consideration of their expression and different regulation in several tissues. |
Databáze: | OpenAIRE |
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