Inhibition of Aryl Hydrocarbon Receptor (AhR) Expression Disrupts Cell Proliferation and Alters Energy Metabolism and Fatty Acid Synthesis in Colon Cancer Cells

KARASOVÁ, Martina, Jiřina PROCHÁZKOVÁ, Zuzana TYLICHOVA, Radek FEDR, Miroslav CIGANEK, Miroslav MACHALA, Zdenek DVORAK, Barbora VYHLIDALOVA, Iveta ZUVALOVA, Jiri EHRMANN, Jan BOUCHAL, Zdeněk ANDRYSÍK and Jan VONDRÁČEK. Inhibition of Aryl Hydrocarbon Receptor (AhR) Expression Disrupts Cell Proliferation and Alters Energy Metabolism and Fatty Acid Synthesis in Colon Cancer Cells. Advances in Gastrointestinal Cancers. BASEL: Mediscript Ltd., 2022, vol. 14, No 17, 20 pp. ISSN 1479-9995. Available from: https://dx.doi.org/10.3390/cancers14174245.

Basic information

• Original name: Inhibition of Aryl Hydrocarbon Receptor (AhR) Expression Disrupts Cell Proliferation and Alters Energy Metabolism and Fatty Acid Synthesis in Colon Cancer Cells
• Authors: KARASOVÁ, Martina, Jiřina PROCHÁZKOVÁ, Zuzana TYLICHOVA, Radek FEDR, Miroslav CIGANEK, Miroslav MACHALA, Zdenek DVORAK, Barbora VYHLIDALOVA, Iveta ZUVALOVA, Jiri EHRMANN, Jan BOUCHAL, Zdeněk ANDRYSÍK and Jan VONDRÁČEK.
• Edition: Advances in Gastrointestinal Cancers, BASEL, Mediscript Ltd. 2022, 1479-9995.

Other information

• Type of outcome: Article in a journal
• Confidentiality degree: is not subject to a state or trade secret
• Doi: http://dx.doi.org/10.3390/cancers14174245
• UT WoS: 000851053900001
• Keywords in English: colon cancer cells; AhR; metabolism; proliferation; fatty acid synthesis; Akt pathway

Abstract

Simple Summary Cancer cells undergo metabolic modifications in order to meet their high energetic demand. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcriptional factor primarily known as a xenobiotic sensor. However, this receptor seems to have a wide range of physiological roles in many processes including cell proliferation, migration or control of immune responses. AhR is often overexpressed in tumor cells of various tissue origin, and several studies have indicated that AhR may also contribute to regulation of cellular metabolism, including synthesis of fatty acids (FA), one of the major steps in metabolic transition. Potential links between the AhR and the control of tumor cell proliferation and metabolism thus deserve more attention. 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.