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
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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