The potential of aryl hydrocarbon receptor as receptors for metabolic changes in tumors

Abstract

Cancer cells can alter their metabolism to meet energy and molecular requirements due to unfavorable environments with oxygen and nutritional deficiencies. Therefore, metabolic reprogramming is common in a tumor microenvironment (TME). Aryl hydrocarbon receptor (AhR) is a ligand-activated nuclear transcription factor, which can be activated by many exogenous and endogenous ligands. Multiple AhR ligands can be produced by both TME and tumor cells. By attaching to various ligands, AhR regulates cancer metabolic reprogramming by dysregulating various metabolic pathways, including glycolysis, lipid metabolism, and nucleotide metabolism. These regulated pathways greatly contribute to cancer cell growth, metastasis, and evading cancer therapies; however, the underlying mechanisms remain unclear. Herein, we review the relationship between TME and metabolism and describe the important role of AhR in cancer regulation. We also focus on recent findings to discuss the idea that AhR acts as a receptor for metabolic changes in tumors, which may provide new perspectives on the direction of AhR research in tumor metabolic reprogramming and future therapeutic interventions.