Compelling evidence has demonstrated that tumor bulk comprises distinctive subset of cells generally referred as cancer stem cells (CSCs) that have been proposed as a strong sustainer and promoter of tumorigenesis and therapeutic resistance. These distinguished properties of CSCs have raised interest in understanding the molecular mechanisms that govern the maintenance of these cells. Numerous experimental and epidemiological studies have demonstrated that exposure to environmental toxins such as the polycyclic aromatic hydrocarbons (PAHs) is strongly involved in cancer initiation and progression. The PAH-induced carcinogenesis is shown to be mediated through the activation of a cytosolic receptor, aryl hydrocarbon receptor (AhR)/Cytochrome P4501A pathway, suggesting a possible direct link between AhR and CSCs. Several recent studies have investigated the role of AhR in CSCs self-renewal and maintenance, however the molecular mechanisms and particularly the epigenetic regulations of CSCs by the AhR/CYP1A pathway have not been reviewed before. In this review, we first summarize the crosstalk between AhR and cancer genetics, with a particular emphasis on the mechanisms relevant to CSCs such as Wnt/β-catenin, Notch, NF-κB, and PTEN-PI3K/Akt signaling pathways. The second part of this review discusses the recent advances and studies highlighting the epigenetic mechanisms mediated by the AhR/CYP1A pathway that control CSC gene expression, self-renewal, and chemoresistance in various human cancers. Furthermore, the review also sheds light on the importance of targeting the epigenetic pathways as a novel therapeutic approach against CSCs.

令人信服的证据表明，肿瘤体积包含通常被称为癌症干细胞 (CSC) 的独特细胞亚群，这些细胞被认为是肿瘤发生和治疗抗性的强大维持者和促进者。CSC 的这些显着特性引起了人们对理解控制这些细胞维持的分子机制的兴趣。大量的实验和流行病学研究表明，暴露于环境毒素如多环芳烃 (PAH) 与癌症的发生和发展密切相关。PAH 诱导的致癌作用被证明是通过激活胞质受体、芳烃受体 (AhR)/细胞色素 P4501A 途径介导的，这表明 AhR 和 CSC 之间可能存在直接联系。最近的几项研究已经调查了 AhR 在 CSC 自我更新和维持中的作用，但是之前尚未审查过 AhR/CYP1A 通路对 CSC 的分子机制，特别是表观遗传调控。在这篇综述中，我们首先总结了 AhR 与癌症遗传学之间的串扰，特别强调了与 CSC 相关的机制，例如 Wnt/β-catenin、Notch、NF-κB 和 PTEN-PI3K/Akt 信号通路。本综述的第二部分讨论了最近的进展和研究，重点介绍了由 AhR/CYP1A 通路介导的表观遗传机制，这些机制控制着各种人类癌症中的 CSC 基因表达、自我更新和化学抗性。此外，该综述还阐明了将表观遗传途径作为针对 CSC 的新型治疗方法的重要性。