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      The controversial role of Enterococcus faecalis in colorectal cancer

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          Abstract

          Colorectal cancer (CRC) is a complex and widespread disease, currently ranked as the third most frequent cancer worldwide. It is well known that the gut microbiota has an essential role in the initiation and promotion of different cancer types, particularly gastrointestinal tumors. In fact, bacteria can trigger chronic inflammation of the gastric mucosal, which can induce irreversible changes to intestinal epithelial cells, thus predisposing individuals to cancer. Some bacterial strains, such as Helicobacter pylori, Streptococcus bovis, Bacteroides fragilis, Clostridium septicum and Fusobacterium spp. have a well established role in CRC development. However, the role of Enterococcus faecalis still remains controversial. While part of the literature suggests a harmful role, other papers reported E. faecalis as an important probiotic microorganism, with great applicability in food products. In this review we have examined the vast majority of published data about E. faecalis either in CRC development or concerning its protective role. Our analysis should provide some answers regarding the controversial role of E. faecalis in CRC.

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          A genetic model for colorectal tumorigenesis.

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            Molecular genetics of colorectal cancer.

            Over the past three decades, molecular genetic studies have revealed some critical mutations underlying the pathogenesis of the sporadic and inherited forms of colorectal cancer (CRC). A relatively limited number of oncogenes and tumor-suppressor genes-most prominently the APC, KRAS, and p53 genes-are mutated in a sizeable fraction of CRCs, and a larger collection of genes that are mutated in subsets of CRC have begun to be defined. Together with DNA-methylation and chromatin-structure changes, the mutations act to dysregulate conserved signaling networks that exert context-dependent effects on critical cell phenotypes, including the regulation of cellular metabolism, proliferation, differentiation, and survival. Much work remains to be done to fully understand the nature and significance of the individual and collective genetic and epigenetic defects in CRC. Some key concepts for the field have emerged, two of which are emphasized in this review. Specifically, the gene defects in CRC often target proteins and pathways that exert pleiotropic effects on the cancer cell phenotype, and particular genetic and epigenetic alterations are linked to biologically and clinically distinct subsets of CRC.
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              Epithelial-cell recognition of commensal bacteria and maintenance of immune homeostasis in the gut.

              Mucosal surfaces such as the intestinal tract are continuously exposed to both potential pathogens and beneficial commensal microorganisms. This creates a requirement for a homeostatic balance between tolerance and immunity that represents a unique regulatory challenge to the mucosal immune system. Recent findings suggest that intestinal epithelial cells, although once considered a simple physical barrier, are a crucial cell lineage for maintaining intestinal immune homeostasis. This Review discusses recent findings that identify a cardinal role for epithelial cells in sampling the intestinal microenvironment, discriminating pathogenic and commensal microorganisms and influencing the function of antigen-presenting cells and lymphocytes.
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                Author and article information

                Contributors
                Journal
                Therap Adv Gastroenterol
                Therap Adv Gastroenterol
                TAG
                sptag
                Therapeutic Advances in Gastroenterology
                SAGE Publications (Sage UK: London, England )
                1756-283X
                1756-2848
                26 June 2018
                2018
                : 11
                : 1756284818783606
                Affiliations
                [1-1756284818783606]Department of Surgery and Translational Medicine, University of Florence, Florence, Italy
                [2-1756284818783606]Department of Surgery and Translational Medicine, University of Florence, Florence, Italy
                [3-1756284818783606]Department of Experimental and Clinical Medicine, University of Florence, Viale Pieraccini, 6, 50139 Florence, Italy
                Author notes
                Article
                10.1177_1756284818783606
                10.1177/1756284818783606
                6044108
                30013618
                13071450-d25c-4fe0-9874-78321a8d1c96
                © The Author(s), 2018

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 2 January 2018
                : 17 May 2018
                Funding
                Funded by: Ente Cassa di Risparmio di Firenze, FundRef https://doi.org/10.13039/501100003056;
                Award ID: 4042.16092014.066000071
                Categories
                Review
                Custom metadata
                January-December 2018

                chronic inflammation,colorectal cancer,enterococcus faecalis,gastrointestinal cancer,gut microbiota

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