Toll-like receptor signaling in colorectal cancer: carcinogenesis to cancer therapy
Toll-like receptor signaling in colorectal cancer: carcinogenesis to cancer therapy
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DOI：
10.3748/wjg.v20.i47.17699
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发表时间：
2014-12-21
影响因子：
4.3
通讯作者：
Qian, Zhi Rong
中科院分区：
文献类型：
--
作者：
Li, Ting-Ting;Ogino, Shuji;Qian, Zhi Rong
Toll样受体（TLR）是种系编码的先天免疫传感器，其识别保守的微生物结构和宿主警报素，并通过巨噬细胞、中性粒细胞、树突状细胞和其他细胞类型发出主要组织相容性复合物蛋白、共刺激分子和炎症介质的信号表达。这些蛋白质受体的特征在于其通过识别特定TLR配体（包括细菌的鞭毛蛋白和脂多糖、源自病毒的核酸和真菌的酵母聚糖）而迅速响应入侵病原体的能力。有2种主要的TLR途径;一种由髓样分化因子88（MYD 88）衔接蛋白介导，另一种不依赖于MYD 88。MYD 88依赖性途径涉及B细胞中κ轻链多肽基因增强子1（NF-κ B1）的核因子的早期激活，并且除TLR 3之外的所有TLR均已显示激活该途径。TLR 3和TLR 4通过MYD 88非依赖性途径起作用，具有NF-κ B信号传导的延迟激活。TLR在激活免疫应答中起着至关重要的作用。TLR已被证明介导炎症反应并维持上皮屏障稳态，并且极有可能参与癌症治疗后许多途径的激活。结直肠癌（CRC）是最常见的癌症之一，并且每年在全世界造成近50万人死亡。炎症被认为是许多常见恶性肿瘤的危险因素，包括结肠直肠癌。参与炎症驱动的致癌作用的关键分子包括TLR。作为细胞死亡和组织重塑的传感器，TLR可能在癌症中具有普遍作用;刺激TLR以激活先天免疫系统多年来一直是一种合理的治疗策略。TLR 3/4/7/8/9都是癌症治疗的有效靶点，许多公司正在开发激动剂和疫苗佐剂。另一方面，拮抗剂可能有利于抑制负责自身免疫反应的信号传导。本文就TLR信号通路在结直肠癌发生、发展和治疗中的作用作一综述。(C)2014百世登出版集团股份有限公司All rights reserved.
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-kappa B1) 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-kappa B 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. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.