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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F22%3A00561061" target="_blank" >RIV/68081707:_____/22:00561061 - isvavai.cz</a>

Alternative codes found

RIV/00027162:_____/22:N0000084 RIV/00159816:_____/22:00077683 RIV/61989592:15310/22:73613657 RIV/00098892:_____/22:10157745 RIV/00216224:14310/22:00127670

Result on the web

<a href="https://www.mdpi.com/2072-6694/14/17/4245" target="_blank" >https://www.mdpi.com/2072-6694/14/17/4245</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/cancers14174245" target="_blank" >10.3390/cancers14174245</a>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30204 - Oncology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2022

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Cancers (Basel)

ISSN

2072-6694

e-ISSN

2072-6694

Volume of the periodical

14

Issue of the periodical within the volume

17

Country of publishing house

CH - SWITZERLAND

Number of pages

20

Pages from-to

4245

UT code for WoS article

000851053900001

EID of the result in the Scopus database

2-s2.0-85137822319