title: Toll-like receptor signaling in colorectal cancer: carcinogenesis to cancer therapy.
abstract: Toll-like receptors (TLRs) are germ line encoded innate immune sensors that recognize conserved microbial structures and host alarmins, and signal expression of major histocompatibility complex proteins, costimulatory molecules, and inflammatory mediators by macrophages, neutrophils, dendritic cells, and other cell types. These protein receptors are characterized by their ability to respond to invading pathogens promptly by recognizing particular TLR ligands, including flagellin and lipopolysaccharide of bacteria, nucleic acids derived from viruses, and zymosan of fungi. There are 2 major TLR pathways; one is mediated by myeloid differentiation factor 88 (MYD88) adaptor proteins, and the other is independent of MYD88. The MYD88-dependent pathway involves early-phase activation of nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (NF-κB1) and all the TLRs, except TLR3, have been shown to activate this pathway. TLR3 and TLR4 act via MYD88-independent pathways with delayed activation of NF-κB signaling. TLRs play a vital role in activating immune responses. TLRs have been shown to mediate inflammatory responses and maintain epithelial barrier homeostasis, and are highly likely to be involved in the activation of a number of pathways following cancer therapy. Colorectal cancer (CRC) is one of the most common cancers, and accounts for almost half a million deaths annually worldwide. Inflammation is considered a risk factor for many common malignancies including cancers of the colorectum. The key molecules involved in inflammation-driven carcinogenesis include TLRs. As sensors of cell death and tissue remodeling, TLRs may have a universal role in cancer; stimulation of TLRs to activate the innate immune system has been a legitimate therapeutic strategy for some years. TLRs 3/4/7/8/9 are all validated targets for cancer therapy, and a number of companies are developing agonists and vaccine adjuvants. On the other hand, antagonists may favor inhibition of signaling responsible for autoimmune responses. In this paper, we review TLR signaling in CRC from carcinogenesis to cancer therapy.
authors.affiliation: Ting-Ting Li, Department of Geriatric Gastroenterology, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Li
authors.affiliation: Ting-Ting Li, Department of Geriatric Gastroenterology, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Shuji
authors.initials: S
authors.lastname: Ogino
authors.affiliation: Ting-Ting Li, Department of Geriatric Gastroenterology, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Zhi Rong
authors.initials: ZR
authors.lastname: Qian
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000627:therapeutic use; D002471:Cell Transformation, Neoplastic / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D015398:Signal Transduction / Q000187:drug effects; D051193:Toll-Like Receptors / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D018836:Inflammation Mediators; D051193:Toll-Like Receptors
keywords: Cancer therapy; Carcinogenesis; Colorectal cancer; Prognosis; Toll-like receptor