How the AHR Became Important in Cancer: The Role of Chronically Active AHR in Cancer Aggression.

Zhongyan Wang,Megan Snyder,Olga Novikov,Jessica E Kenison,Kawtar Bennani,Brian Lara,Emily Lydell,Stefano Monti,David H Sherr,Anthony Federico,Kangkang Yang

doi:10.3390/ijms22010387

Abstract

For decades, the aryl hydrocarbon receptor (AHR) was studied for its role in environmental chemical toxicity i.e., as a quirk of nature and a mediator of unintended consequences of human pollution. During that period, it was not certain that the AHR had a “normal” physiological function. However, the ongoing accumulation of data from an ever-expanding variety of studies on cancer, cancer immunity, autoimmunity, organ development, and other areas bears witness to a staggering array of AHR-controlled normal and pathological activities. The objective of this review is to discuss how the AHR has gone from a likely contributor to genotoxic environmental carcinogen-induced cancer to a master regulator of malignant cell progression and cancer aggression. Particular focus is placed on the association between AHR activity and poor cancer outcomes, feedback loops that control chronic AHR activity in cancer, and the role of chronically active AHR in driving cancer cell invasion, migration, cancer stem cell characteristics, and survival.

Highlights

Highercancers expression in human cancers of the genes driven by baseline significantly correlated with poorer survival in all eight knockout significantly correlated with poorer cancer types
We have summarized a variety of studies, all of which rest on a foundation of toxicological research that was designed to define the basic molecular mechanisms through which environmental aryl hydrocarbon receptor (AHR) ligands generate adverse biological responses
The results clearly indicate a complex association between the AHR and several critical cancer features, including increased malignant cell invasion, migration, metastasis, Cancer Stem Cell (CSC) formation, and survival

Summary

Introduction

The aryl hydrocarbon receptor (AHR) was studied for its role in environmental chemical toxicity i.e., as a quirk of nature and a mediator of unintended consequences of human pollution. The ongoing accumulation of data from an ever-expanding variety of studies on cancer, cancer immunity, autoimmunity, organ development, and other areas bears witness to a staggering array of AHR-controlled normal and pathological activities. The objective of this review is to discuss how the AHR has gone from a likely contributor to genotoxic environmental carcinogen-induced cancer to a master regulator of malignant cell progression and cancer aggression. Particular focus is placed on the association between AHR activity and poor cancer outcomes, feedback loops that control chronic AHR activity in cancer, and the role of chronically active AHR in driving cancer cell invasion, migration, cancer stem cell characteristics, and survival.

Objectives

Methods

Findings

Conclusion