The aryl hydrocarbon receptor (AhR) plays a wide range of physiological roles in cellular processes such as proliferation, migration or control of immune responses. Several studies have also indicated that AhR might contribute to the regulation of energy balance or cellular metabolism. We observed that the AhR is upregulated in tumor epithelial cells derived from colon cancer patients. Using wild-type and the corresponding AhR knockout (AhR KO) variants of human colon cancer cell lines HCT116 and HT-29, we analyzed possible role(s) of the AhR in cell proliferation and metabolism, with a focus on regulation of the synthesis of fatty acids (FAs). We observed a decreased proliferation rate in the AhR KO cells, which was accompanied with altered cell cycle progression, as well as a decreased ATP production. We also found reduced mRNA levels of key enzymes of the FA biosynthetic pathway in AhR KO colon cancer cells, in particular of stearoyl-CoA desaturase 1 (SCD1). The loss of AhR was also associated with reduced expression and/or activity of components of the PI3K/Akt pathway, which controls lipid metabolism, and other lipogenic transcriptional regulators, such as sterol regulatory element binding transcription factor 1 (SREBP1). Together, our data indicate that disruption of AhR activity in colon tumor cells may, likely in a cell-specific manner, limit their proliferation, which could be linked with a suppressive effect on their endogenous FA metabolism. More attention should be paid to potential mechanistic links between overexpressed AhR and colon tumor cell metabolism.

Department of Cell Biology and Genetics Faculty of Science Palacký University 78371 Olomouc Czech Republic

Department of Clinical and Molecular Pathology Institute of Molecular and Translational Medicine Faculty of Medicine Palacký University and University Hospital 77900 Olomouc Czech Republic

Department of Cytokinetics Institute of Biophysics of the Czech Academy of Sciences 61265 Brno Czech Republic

Department of Experimental Biology Faculty of Science Masaryk University 62500 Brno Czech Republic

Department of Pharmacology and Toxicology Veterinary Research Institute 62100 Brno Czech Republic

Department of Pharmacology School of Medicine University of Colorado Anschutz Medical Campus Aurora CO 80045 USA

International Clinical Research Center St Anne's University Hospital Brno 65691 Brno Czech Republic

Linda Crnic Institute for Down Syndrome School of Medicine University of Colorado Anschutz Medical Campus Aurora CO 80045 USA

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