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.
2021
Hofmanová, Jiřina; Slavík, Josef; Ciganek, Miroslav; Ovesná, Petra; Tylichová, Zuzana; Karasová, Martina; Zapletal, Ondřej; Straková, Nicol; Procházková, Jiřina; Bouchal, Jan; Kolář, Zdeněk; Ehrmann, Jiří; Levková, Monika; Hušková, Zlatka; Skalický, Pavel; Kozubík, Alois; Machala, Miroslav; Vondráček, Jan
Complex Alterations of Fatty Acid Metabolism and Phospholipidome Uncovered in Isolated Colon Cancer Epithelial Cells. Journal Article
In: International journal of molecular sciences, vol. 22, no. 13, 2021, ISSN: 1422-0067, (Place: Switzerland).
Abstract | Links | BibTeX | Tags: *Gene Expression Regulation, *Lipid Metabolism, Adenocarcinoma/enzymology/genetics/*metabolism, Aged, Colonic Neoplasms/enzymology/genetics/*metabolism, colorectal carcinoma, desaturation, EpCAM, Epithelial Cells, Epithelial Cells/enzymology/metabolism, Fatty Acid Desaturases/genetics/metabolism, Fatty Acid Elongases/genetics/metabolism, Fatty Acid Synthases/genetics/metabolism, fatty acid synthesis, Fatty Acids/*metabolism, Female, Humans, lipidomics, Lipogenesis, lysophospholipids, Male, Neoplastic, Phospholipids, Phospholipids/*metabolism, Stearoyl-CoA Desaturase/genetics/metabolism
@article{hofmanova_complex_2021,
title = {Complex Alterations of Fatty Acid Metabolism and Phospholipidome Uncovered in Isolated Colon Cancer Epithelial Cells.},
author = {Jiřina Hofmanová and Josef Slavík and Miroslav Ciganek and Petra Ovesná and Zuzana Tylichová and Martina Karasová and Ondřej Zapletal and Nicol Straková and Jiřina Procházková and Jan Bouchal and Zdeněk Kolář and Jiří Ehrmann and Monika Levková and Zlatka Hušková and Pavel Skalický and Alois Kozubík and Miroslav Machala and Jan Vondráček},
doi = {10.3390/ijms22136650},
issn = {1422-0067},
year = {2021},
date = {2021-06-01},
journal = {International journal of molecular sciences},
volume = {22},
number = {13},
abstract = {The development of colon cancer, one of the most common malignancies, is accompanied with numerous lipid alterations. However, analyses of whole tumor samples may not always provide an accurate description of specific changes occurring directly in tumor epithelial cells. Here, we analyzed in detail the phospholipid (PL), lysophospholipid (lysoPL), and fatty acid (FA) profiles of purified EpCAM(+) cells, isolated from tumor and adjacent non-tumor tissues of colon cancer patients. We found that a number of FAs increased significantly in isolated tumor cells, which also included a number of long polyunsaturated FAs. Higher levels of FAs were associated with increased expression of FA synthesis genes, as well as with altered expression of enzymes involved in FA elongation and desaturation, including particularly fatty acid synthase, stearoyl-CoA desaturase, fatty acid desaturase 2 and ELOVL5 fatty acid elongase 5 We identified significant changes in ratios of specific lysoPLs and corresponding PLs. A number of lysophosphatidylcholine and lysophosphatidylethanolamine species, containing long-chain and very-long chain FAs, often with high numbers of double bonds, were significantly upregulated in tumor cells. Increased de novo synthesis of very long-chain FAs, or, altered uptake or incorporation of these FAs into specific lysoPLs in tumor cells, may thus contribute to reprogramming of cellular phospholipidome and membrane alterations observed in colon cancer.},
note = {Place: Switzerland},
keywords = {*Gene Expression Regulation, *Lipid Metabolism, Adenocarcinoma/enzymology/genetics/*metabolism, Aged, Colonic Neoplasms/enzymology/genetics/*metabolism, colorectal carcinoma, desaturation, EpCAM, Epithelial Cells, Epithelial Cells/enzymology/metabolism, Fatty Acid Desaturases/genetics/metabolism, Fatty Acid Elongases/genetics/metabolism, Fatty Acid Synthases/genetics/metabolism, fatty acid synthesis, Fatty Acids/*metabolism, Female, Humans, lipidomics, Lipogenesis, lysophospholipids, Male, Neoplastic, Phospholipids, Phospholipids/*metabolism, Stearoyl-CoA Desaturase/genetics/metabolism},
pubstate = {published},
tppubtype = {article}
}
The development of colon cancer, one of the most common malignancies, is accompanied with numerous lipid alterations. However, analyses of whole tumor samples may not always provide an accurate description of specific changes occurring directly in tumor epithelial cells. Here, we analyzed in detail the phospholipid (PL), lysophospholipid (lysoPL), and fatty acid (FA) profiles of purified EpCAM(+) cells, isolated from tumor and adjacent non-tumor tissues of colon cancer patients. We found that a number of FAs increased significantly in isolated tumor cells, which also included a number of long polyunsaturated FAs. Higher levels of FAs were associated with increased expression of FA synthesis genes, as well as with altered expression of enzymes involved in FA elongation and desaturation, including particularly fatty acid synthase, stearoyl-CoA desaturase, fatty acid desaturase 2 and ELOVL5 fatty acid elongase 5 We identified significant changes in ratios of specific lysoPLs and corresponding PLs. A number of lysophosphatidylcholine and lysophosphatidylethanolamine species, containing long-chain and very-long chain FAs, often with high numbers of double bonds, were significantly upregulated in tumor cells. Increased de novo synthesis of very long-chain FAs, or, altered uptake or incorporation of these FAs into specific lysoPLs in tumor cells, may thus contribute to reprogramming of cellular phospholipidome and membrane alterations observed in colon cancer.