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Epigenetic Regulation of Cancer Stem Cells by the Aryl Hydrocarbon Receptor Pathway

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journal contribution
submitted on 2023-10-09, 07:37 and posted on 2023-10-09, 08:13 authored by Sabah Akhtar, Shireen Hourani, Lubna Therachiyil, Abdullah Al-Dhfyan, Abdelali Agouni, Asad Zeidan, Shahab Uddin, Hesham M. Korashy

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.

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Published in: Seminars in Cancer Biology
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Open Access funding provided by the Qatar National Library



  • English



Publication Year

  • 2022

License statement

This Item is licensed under the Creative Commons Attribution 4.0 International License

Institution affiliated with

  • Qatar University
  • Qatar University Health - QU
  • College of Pharmacy - QU HEALTH
  • College of Medicine - QU HEALTH
  • Hamad Medical Corporation
  • Academic Health System - HMC
  • Interim Translational Research Institute - HMC