title: Contribution of TLR signaling to the pathogenesis of colitis-associated cancer in inflammatory bowel disease.
abstract: In the intestine a balance between proinflammatory and repair signals of the immune system is essential for the maintenance of intestinal homeostasis. The innate immunity ensures a primary host response to microbial invasion, which induces an inflammatory process to localize the infection and prevent systemic dissemination of pathogens. The key elements of this process are the germline encoded pattern recognition receptors including Toll-like receptors (TLRs). If pathogens cannot be eliminated, they may elicit chronic inflammation, which may be partly mediated via TLRs. Additionally, chronic inflammation has long been suggested to trigger tissue tumorous transformation. Inflammation, the seventh hallmark of cancer, may affect all phases of tumor development, and evade the immune system. Inflammation acts as a cellular stressor and may trigger DNA damage or genetic instability. Furthermore, chronic inflammation can provoke genetic mutations and epigenetic mechanisms that promote malignant cell transformation. Colorectal cancers in inflammatory bowel disease patients are considered typical examples of inflammation-related cancers. Although data regarding the role of TLRs in the pathomechanism of cancer-associated colitis are rather conflicting, functionally these molecules can be classified as "largely antitumorigenic" and "largely pro-tumorigenic" with the caveat that the underlying signaling pathways are mainly context (i.e., organ-, tissue-, cell-) and ligand-dependent.
authors.affiliation: Ferenc Sipos, István Fűri, Miklós Constantinovits, Györgyi Műzes, 2 Department of Internal Medicine, Semmelweis University, 1088 Budapest, Hungary.
authors.forename: Ferenc
authors.initials: F
authors.lastname: Sipos
authors.affiliation: Ferenc Sipos, István Fűri, Miklós Constantinovits, Györgyi Műzes, 2 Department of Internal Medicine, Semmelweis University, 1088 Budapest, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Fűri
authors.affiliation: Ferenc Sipos, István Fűri, Miklós Constantinovits, Györgyi Műzes, 2 Department of Internal Medicine, Semmelweis University, 1088 Budapest, Hungary.
authors.forename: Miklós
authors.initials: M
authors.lastname: Constantinovits
authors.affiliation: Ferenc Sipos, István Fűri, Miklós Constantinovits, Györgyi Műzes, 2 Department of Internal Medicine, Semmelweis University, 1088 Budapest, Hungary.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Tulassay
authors.affiliation: Ferenc Sipos, István Fűri, Miklós Constantinovits, Györgyi Műzes, 2 Department of Internal Medicine, Semmelweis University, 1088 Budapest, Hungary.
authors.forename: Györgyi
authors.initials: G
authors.lastname: Műzes
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D003092:Colitis / Q000150:complications* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D003110:Colonic Neoplasms / Q000209:etiology* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D018836:Inflammation Mediators; D051193:Toll-Like Receptors
keywords: Carcinogenesis; Colitis-associated cancer; Immunoregulation; Inflammation; Inflammatory bowel disease; Tissue repair; Toll-like receptor