2022
Karasová, Martina; Procházková, Jiřina; Tylichová, Zuzana; Fedr, Radek; Ciganek, Miroslav; Machala, Miroslav; Dvořák, Zdeněk; Vyhlídalová, Barbora; Zůvalová, Iveta; Ehrmann, Jiří; Bouchal, Jan; Andrysík, Zdeněk; Vondráček, Jan
In: Cancers, vol. 14, no. 17, 2022, ISSN: 2072-6694, (Place: Switzerland).
Abstract | Links | BibTeX | Tags: AhR, Akt pathway, colon cancer cells, fatty acid synthesis, metabolism, proliferation
@article{karasova_inhibition_2022,
title = {Inhibition of Aryl Hydrocarbon Receptor (AhR) Expression Disrupts Cell Proliferation and Alters Energy Metabolism and Fatty Acid Synthesis in Colon Cancer Cells.},
author = {Martina Karasová and Jiřina Procházková and Zuzana Tylichová and Radek Fedr and Miroslav Ciganek and Miroslav Machala and Zdeněk Dvořák and Barbora Vyhlídalová and Iveta Zůvalová and Jiří Ehrmann and Jan Bouchal and Zdeněk Andrysík and Jan Vondráček},
doi = {10.3390/cancers14174245},
issn = {2072-6694},
year = {2022},
date = {2022-08-01},
journal = {Cancers},
volume = {14},
number = {17},
abstract = {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.},
note = {Place: Switzerland},
keywords = {AhR, Akt pathway, colon cancer cells, fatty acid synthesis, metabolism, proliferation},
pubstate = {published},
tppubtype = {article}
}
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.
2019
Machala, Miroslav; Procházková, Jiřina; Hofmanová, Jiřina; Králiková, Lucie; Slavík, Josef; Tylichová, Zuzana; Ovesná, Petra; Kozubík, Alois; Vondráček, Jan
Colon Cancer and Perturbations of the Sphingolipid Metabolism. Journal Article
In: International journal of molecular sciences, vol. 20, no. 23, 2019, ISSN: 1422-0067, (Place: Switzerland).
Abstract | Links | BibTeX | Tags: *Gene Expression Regulation, Acid Ceramidase/genetics/metabolism, Alkaline Ceramidase/genetics/metabolism, Animal, Animals, Ceramides/metabolism, colon cancer (CRC) sphingolipidomics, colon cancer cells, Colonic Neoplasms/*enzymology/genetics/pathology, colorectal cancer, Cultured, Disease Models, glycosphingolipid, Humans, Lactosylceramide, Lactosylceramides/*metabolism, Lipid Metabolism/*genetics, Lysophospholipids/metabolism, Neoplastic, Neutral Ceramidase/genetics/metabolism, Phosphotransferases (Alcohol Group Acceptor)/genetics/metabolism, Proto-Oncogene Proteins c-akt/genetics/metabolism, sphingolipid, Sphingolipids/*metabolism, Sphingosine N-Acyltransferase/genetics/metabolism, sphingosine-1-phosphate, Sphingosine/analogs & derivatives/metabolism, Tumor Cells
@article{machala_colon_2019,
title = {Colon Cancer and Perturbations of the Sphingolipid Metabolism.},
author = {Miroslav Machala and Jiřina Procházková and Jiřina Hofmanová and Lucie Králiková and Josef Slavík and Zuzana Tylichová and Petra Ovesná and Alois Kozubík and Jan Vondráček},
doi = {10.3390/ijms20236051},
issn = {1422-0067},
year = {2019},
date = {2019-11-01},
journal = {International journal of molecular sciences},
volume = {20},
number = {23},
abstract = {The development and progression of colorectal cancer (CRC), a major cause of cancer-related death in the western world, is accompanied with alterations of sphingolipid (SL) composition in colon tumors. A number of enzymes involved in the SL metabolism have been found to be deregulated in human colon tumors, in experimental rodent studies, and in human colon cancer cells in vitro. Therefore, the enzymatic pathways that modulate SL levels have received a significant attention, due to their possible contribution to CRC development, or as potential therapeutic targets. Many of these enzymes are associated with an increased sphingosine-1-phosphate/ceramide ratio, which is in turn linked with increased colon cancer cell survival, proliferation and cancer progression. Nevertheless, more attention should also be paid to the more complex SLs, including specific glycosphingolipids, such as lactosylceramides, which can be also deregulated during CRC development. In this review, we focus on the potential roles of individual SLs/SL metabolism enzymes in colon cancer, as well as on the pros and cons of employing the current in vitro models of colon cancer cells for lipidomic studies investigating the SL metabolism in CRC.},
note = {Place: Switzerland},
keywords = {*Gene Expression Regulation, Acid Ceramidase/genetics/metabolism, Alkaline Ceramidase/genetics/metabolism, Animal, Animals, Ceramides/metabolism, colon cancer (CRC) sphingolipidomics, colon cancer cells, Colonic Neoplasms/*enzymology/genetics/pathology, colorectal cancer, Cultured, Disease Models, glycosphingolipid, Humans, Lactosylceramide, Lactosylceramides/*metabolism, Lipid Metabolism/*genetics, Lysophospholipids/metabolism, Neoplastic, Neutral Ceramidase/genetics/metabolism, Phosphotransferases (Alcohol Group Acceptor)/genetics/metabolism, Proto-Oncogene Proteins c-akt/genetics/metabolism, sphingolipid, Sphingolipids/*metabolism, Sphingosine N-Acyltransferase/genetics/metabolism, sphingosine-1-phosphate, Sphingosine/analogs & derivatives/metabolism, Tumor Cells},
pubstate = {published},
tppubtype = {article}
}
The development and progression of colorectal cancer (CRC), a major cause of cancer-related death in the western world, is accompanied with alterations of sphingolipid (SL) composition in colon tumors. A number of enzymes involved in the SL metabolism have been found to be deregulated in human colon tumors, in experimental rodent studies, and in human colon cancer cells in vitro. Therefore, the enzymatic pathways that modulate SL levels have received a significant attention, due to their possible contribution to CRC development, or as potential therapeutic targets. Many of these enzymes are associated with an increased sphingosine-1-phosphate/ceramide ratio, which is in turn linked with increased colon cancer cell survival, proliferation and cancer progression. Nevertheless, more attention should also be paid to the more complex SLs, including specific glycosphingolipids, such as lactosylceramides, which can be also deregulated during CRC development. In this review, we focus on the potential roles of individual SLs/SL metabolism enzymes in colon cancer, as well as on the pros and cons of employing the current in vitro models of colon cancer cells for lipidomic studies investigating the SL metabolism in CRC.