Abstract：
Aryl hydrocarbon receptor (AHR) is a ligand-dependent receptor that belongs to the superfamily of basic helix-loop-helix (bHLH) transcription factors. The activation of the canonical AHR signaling pathway is known to induce the expression of cytochrome P450 enzymes, facilitating the detoxification metabolism in the human body. Additionally, AHR could interact with various signaling pathways such as epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 3 (STAT3), hypoxia-inducible factor-1α (HIF-1α), nuclear factor ekappa B (NF-κβ), estrogen receptor (ER), and androgen receptor (AR) signaling pathways. Over the past 30 years, several studies have reported that various chemical, physical, or biological agents, such as tobacco, hydrocarbon compounds, industrial and agricultural chemical wastes, drugs, UV, viruses, and other toxins, could affect AHR expression or activity, promoting cancer development. Thus, it is valuable to overview how these factors regulate AHR-mediated carcinogenesis. Current findings have reported that many compounds could act as AHR ligands to drive the expressions of AHR-target genes, such as CYP1A1, CYP1B1, MMPs, and AXL, and other targets that exert a pro-proliferation or anti-apoptotic effect, like XIAP. Furthermore, some other physical and chemical agents, such as UV and 3-methylcholanthrene, could promote AHR signaling activities, increasing the signaling activities of a few oncogenic pathways, such as the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathways. Understanding how various factors regulate AHR-mediated carcinogenesis processes helps clinicians and scientists plan personalized therapeutic strategies to improve anti-cancer treatment efficacy. As many studies that have reported the roles of AHR in regulating carcinogenesis are preclinical or observational clinical studies that did not explore the detailed mechanisms of how different chemical, physical, or biological agents promote AHR-mediated carcinogenesis processes, future studies should focus on conducting large-scale and functional studies to unravel the underlying mechanism of how AHR interacts with different factors in regulating carcinogenesis processes.
摘要：
芳香烃受体（AHR）是一种配体依赖性受体，属于碱性螺旋-环-螺旋（bHLH）转录因子超家族。已知经典AHR信号通路的激活诱导细胞色素P450酶的表达,促进人体内的解毒代谢。此外,AHR可以与多种信号通路相互作用，如表皮生长因子受体（EGFR），信号转导和转录激活因子3（STAT3），缺氧诱导因子-1α(HIF-1α),核因子κB（NF-κβ），雌激素受体(ER),和雄激素受体（AR）信号通路。在过去的30年里,一些研究报告说，各种化学物质，物理，或生物制剂，比如烟草,碳氢化合物，工业和农业化学废物，毒品,UV,病毒,和其他毒素,可能会影响AHR的表达或活动，促进癌症发展。因此，概述这些因素如何调节AHR介导的致癌作用是有价值的。目前的研究发现，许多化合物可以作为AHR配体驱动AHR靶基因的表达，如CYP1A1，CYP1B1，MMPs，和AXL，和其他发挥促增殖或抗凋亡作用的靶标，比如XIAP.此外，一些其他物理和化学制剂，如紫外线和3-甲基胆碱，可以促进AHR信号活动，增加一些致癌途径的信号活性，例如磷脂酰肌醇3-激酶/蛋白激酶B（PI3K/AKT）和丝裂原活化蛋白激酶/细胞外信号调节激酶（MAPK/ERK）途径。了解各种因素如何调节AHR介导的致癌过程有助于临床医生和科学家制定个性化的治疗策略，以提高抗癌治疗效果。由于许多报道了AHR在调节癌变中的作用的研究是临床前或观察性临床研究，没有探讨不同化学物质的详细机制，物理，或生物制剂促进AHR介导的致癌过程，未来的研究应集中在进行大规模和功能性研究,以揭示AHR在调节癌变过程中与不同因素相互作用的潜在机制.
