文章：

癌症中的芳烃受体配体：友与敌

Aryl hydrocarbon receptor ligands in cancer: friend and foe

原文发布日期：2014-11-24

DOI: 10.1038/nrc3846

类型: Review Article

开放获取: 否

要点：

1. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that is best known for mediating the toxicity and tumour-promoting properties of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; commonly referred to as 'dioxin').
2. Three distinct classes of ligands bind to AHR: agonists, antagonists and selective AHR modulators. AHR is activated by endogenous ligands such as kynurenine, kynurenic acid and indoxyl sulphate, and physiologically relevant flora can produce potent AHR ligands from tryptophan.
3. Human AHR and mouse AHR exhibit substantial differences in ligand specificity, which might influence the progression of cancer. This complicates the validity of mouse models for studying the effects of AHR on human carcinogenesis.
4. Numerous studies demonstrate the ability of AHR to increase the proliferative and migratory potential of tumour cells.
5. AHR directly modulates inflammatory signalling, and AHR levels are often increased in tumours, probably as a result of inflammatory signalling. AHR agonist-mediated activity can have a key role in the production of regulatory T cells and thus could have a role in immune tolerance in cancer.

要点翻译：

1. 芳香烃受体（AHR）是一种配体激活的转录因子，其主要以介导2,3,7,8-四氯二苯并-p-二噁英（常称为“二噁英”）的毒性和肿瘤促进特性而闻名。
2. 该受体可结合三类配体：激动剂、拮抗剂和选择性AHR调节剂。AHR能被内源性配体（如犬尿氨酸、犬尿酸和硫酸吲哚酚）激活，且具有生理相关性的菌群能通过色氨酸产生强效AHR配体。
3. 人源AHR与小鼠AHR在配体特异性上存在显著差异，这可能影响癌症的进展。这一特性使得小鼠模型在研究AHR对人类致癌作用时的有效性变得复杂。
4. 大量研究证实AHR能增强肿瘤细胞的增殖和迁移能力。
5. AHR直接调节炎症信号传导，且其水平在肿瘤中常出现升高——这可能是炎症信号传导的结果。AHR激动剂介导的活性在调节性T细胞的生成中起关键作用，因此可能参与癌症中的免疫耐受过程。

英文摘要：

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that is best known for mediating the toxicity and tumour-promoting properties of the carcinogen 2,3,7,8-tetrachlorodibenzo-p-dioxin, commonly referred to as 'dioxin'. AHR influences the major stages of tumorigenesis — initiation, promotion, progression and metastasis — and physiologically relevant AHR ligands are often formed during disease states or during heightened innate and adaptive immune responses. Interestingly, ligand specificity and affinity vary between rodents and humans. Studies of aggressive tumours and tumour cell lines show increased levels of AHR and constitutive localization of this receptor in the nucleus. This suggests that the AHR is chronically activated in tumours, thus facilitating tumour progression. This Review discusses the role of AHR in tumorigenesis and the potential for therapeutic modulation of its activity in tumours.

摘要翻译： 

芳烃受体（AHR）是一种配体激活的转录因子，最著名的是介导致癌物2,3,7,8-四氯二苯并-对-二噁英（通常称为“二噁英”）的毒性和促肿瘤特性。AHR影响肿瘤发生的主要阶段——起始、促进、进展和转移——并且在疾病状态或先天与适应性免疫反应增强期间，常形成生理相关的AHR配体。有趣的是，啮齿动物与人类之间的配体特异性和亲和力存在差异。对侵袭性肿瘤和肿瘤细胞系的研究显示，AHR水平升高，且该受体在细胞核中呈持续性定位。这表明AHR在肿瘤中被慢性激活，从而促进肿瘤进展。本综述讨论了AHR在肿瘤发生中的作用，以及在治疗中调节其活性的潜力。

原文链接：

Aryl hydrocarbon receptor ligands in cancer: friend and foe