Aryl Hydrocarbon Receptor Connects Inflammation to Breast Cancer

Int J Mol Sci. 2020 Jul 24;21(15):5264. doi: 10.3390/ijms21155264.

Abstract

Aryl hydrocarbon receptor (AhR), an evolutionary conserved transcription factor, is a pleiotropic signal transductor. Thanks to its promiscuous ligand binding domain, during the evolution of eukaryotic cells its developmental functions were integrated with biosensor functions. Its activation by a multitude of endogenous and exogenous molecules stimulates its participation in several pathways, some of which are linked to inflammation and breast cancer (BC). Over time, the study of this malignancy has led to the identification of several therapeutic targets in cancer cells. An intense area of study is dedicated to BC phenotypes lacking adequate targets. In this context, due to its high constitutive activation in BC, AhR is currently gaining more and more attention. In this review, I have considered its interactions with: 1. the immune system, whose dysregulation is a renowned cancer hallmark; 2. interleukin 6 (IL6) which is a pivotal inflammatory marker and is closely correlated to breast cancer risk; 3. NF-kB, another evolutionary conserved transcription factor, which plays a key role in immunoregulatory functions, inflammatory response and breast carcinogenesis; 4. kynurenine, a tryptophan-derived ligand that activates and bridges AhR to chronic inflammation and breast carcinogenesis. Overall, the data here presented form an interesting framework where AhR is an interesting connector between inflammation and BC.

Keywords: aryl hydrocarbon receptor; breast cancer; inflammation.

Publication types

  • Review

MeSH terms

  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Carcinogenesis / genetics
  • Carcinogenesis / metabolism*
  • Female
  • Humans
  • Inflammation / genetics
  • Inflammation / metabolism
  • Inflammation / pathology
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / metabolism*

Substances

  • AHR protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • Neoplasm Proteins
  • Receptors, Aryl Hydrocarbon