Complex Alterations of Fatty Acid Metabolism and Phospholipidome Uncovered in Isolated Colon Cancer Epithelial Cells.

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.

• Authors: Jiřina Hofmanová, Josef Slavík, Miroslav Ciganek, Petra Ovesná, Zuzana Tylichová, Martina Karasová, Ondřej Zapletal, Nicol Straková, Jiřina Procházková, Jan Bouchal, Zdeněk Kolář, Jiří Ehrmann, Monika Levková, Zlatka Hušková, Pavel Skalický, Alois Kozubík, Miroslav Machala, Jan Vondráček
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 22 Issue 13 (Jun 22 2021) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 34206240 (Publication Type: Journal Article)

Chemical References

• ELOVL5 protein, human
• Fatty Acids
• Phospholipids
• Fatty Acid Desaturases
• Stearoyl-CoA Desaturase
• FADS2 protein, human
• Fatty Acid Elongases
• Fatty Acid Synthases

Topics

• Adenocarcinoma (enzymology, genetics, metabolism)
• Aged
• Colonic Neoplasms (enzymology, genetics, metabolism)
• Epithelial Cells (enzymology, metabolism)
• Fatty Acid Desaturases (genetics, metabolism)
• Fatty Acid Elongases (genetics, metabolism)
• Fatty Acid Synthases (genetics, metabolism)
• Fatty Acids (metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Lipid Metabolism
• Lipidomics
• Lipogenesis
• Male
• Phospholipids (metabolism)
• Stearoyl-CoA Desaturase (genetics, metabolism)