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      Linking Gut Microbiota to Colorectal Cancer

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          Abstract

          Pre-clinical and clinical data produce mounting evidence that the microbiota is strongly associated with colorectal carcinogenesis. Dysbiosis may change the course of carcinogenesis as microbial actions seem to impact genetic and epigenetic alterations leading to dysplasia, clonal expansion and malignant transformation. Initiation and promotion of colorectal cancer may result from direct bacterial actions, bacterial metabolites and inflammatory pathways. Newer aspects of microbiota and colorectal cancer include quorum sensing, biofilm formation, sidedness and effects/countereffects of microbiota and probiotics on chemotherapy. In the future, targeting the microbiota will probably be a powerful weapon in the battle against CRC as gut microbiology, genomics and metabolomics promise to uncover important linkages between microbiota and intestinal health.

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          Most cited references90

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          A genetic model for colorectal tumorigenesis.

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            How glycan metabolism shapes the human gut microbiota.

            Symbiotic microorganisms that reside in the human intestine are adept at foraging glycans and polysaccharides, including those in dietary plants (starch, hemicellulose and pectin), animal-derived cartilage and tissue (glycosaminoglycans and N-linked glycans), and host mucus (O-linked glycans). Fluctuations in the abundance of dietary and endogenous glycans, combined with the immense chemical variation among these molecules, create a dynamic and heterogeneous environment in which gut microorganisms proliferate. In this Review, we describe how glycans shape the composition of the gut microbiota over various periods of time, the mechanisms by which individual microorganisms degrade these glycans, and potential opportunities to intentionally influence this ecosystem for better health and nutrition.
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              Dependency of colorectal cancer on a TGF-β-driven program in stromal cells for metastasis initiation.

              A large proportion of colorectal cancers (CRCs) display mutational inactivation of the TGF-β pathway, yet, paradoxically, they are characterized by elevated TGF-β production. Here, we unveil a prometastatic program induced by TGF-β in the microenvironment that associates with a high risk of CRC relapse upon treatment. The activity of TGF-β on stromal cells increases the efficiency of organ colonization by CRC cells, whereas mice treated with a pharmacological inhibitor of TGFBR1 are resilient to metastasis formation. Secretion of IL11 by TGF-β-stimulated cancer-associated fibroblasts (CAFs) triggers GP130/STAT3 signaling in tumor cells. This crosstalk confers a survival advantage to metastatic cells. The dependency on the TGF-β stromal program for metastasis initiation could be exploited to improve the diagnosis and treatment of CRC. Copyright © 2012 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                J Cancer
                J Cancer
                jca
                Journal of Cancer
                Ivyspring International Publisher (Sydney )
                1837-9664
                2017
                20 September 2017
                : 8
                : 17
                : 3378-3395
                Affiliations
                [1 ]Speciallægecentret ved Diakonissestiftelsen, Frederiksberg, Denmark;
                [2 ]Department of Surgery, Zealand University Hospital, University of Copenhagen, Denmark;
                [3 ]Department of Surgical Gastroenterology, Rigshospitalet, Copenhagen, Denmark.
                Author notes
                ✉ Corresponding author: Hans Raskov, MD., Lundevangsvej 23, DK-2900 Hellerup, Denmark Phone: +45 2441 4031 Email: raskov@ 123456mail.dk

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                jcav08p3378
                10.7150/jca.20497
                5687151
                29151921
                cdf13b16-ce78-4f05-9130-b18a4ca3d5bb
                © Ivyspring International Publisher

                This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.

                History
                : 10 April 2017
                : 10 August 2017
                Categories
                Review

                Oncology & Radiotherapy
                microbiota,dysbiosis,mucosal defense mechanisms,inflammation,carcinogenesis,colorectal cancer.

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