mTOR Signaling and SREBP Activity Increase FADS2 Expression and Can Activate Sapienate Biosynthesis

Triki, Mouna; Rinaldi, Gianmarco; Planque, Mélanie; Broekaert, Dorien; Winkelkotte, Alina M; Maier, Carina R.; Raman, Sudha Janaki; Vandekeere, Anke; Elsen, Joke Van; Orth, Martin F.; Grünewald, Thomas G.P.; Schulze, Almut; Fendt, Sarah-Maria

doi:10.1016/j.celrep.2020.107806

Cited by 43 publications

(33 citation statements)

References 45 publications

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“…Interestingly, FADS2 is an enzyme involved in arachidonic acid production, and it may promote prostaglandin E2 production in colon tumor cells, which could be linked with increased colon cancer cell proliferation [47]. FADS2 may also contribute to production of a much wider spectrum of FAs in cancer cells as compared with their normal counterparts [48,49].…”

Section: Discussionmentioning

confidence: 99%

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

Hofmanová

Slavík

Cigánek

et al. 2021

IJMS

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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.

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Section: Discussionmentioning

confidence: 99%

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

Hofmanová

Slavík

Cigánek

et al. 2021

IJMS

View full text Add to dashboard Cite

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“…Contrary to human lung (Hensley et al , ) and brain tumors (Maher et al , ), which show significant levels of glucose oxidation, tumors growing in the kidney display enhanced glycolytic flux with minimal glucose oxidation and turnover of the TCA cycle (Courtney et al , ). Cancer cells growing in the liver can also rewire palmitate metabolism by desaturating palmitate using fatty acid desaturase 2 (FADS2) to the unusual fatty acid sapienate which can potentially influence oncogenic lipid‐signaling networks (Vriens et al , ; Triki et al , ), suggesting an alternative mechanism of metabolic plasticity triggered by fatty acid metabolism.…”

Section: Introductionmentioning

confidence: 99%

Nutrient metabolism and cancer in the in vivo context: a metabolic game of give and take

et al. 2020

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Nutrients are indispensable resources that provide the macromolecular building blocks and energy requirements for sustaining cell growth and survival. Cancer cells require several key nutrients to fulfill their changing metabolic needs as they progress through stages of development. Moreover, both cell-intrinsic and microenvironment-influenced factors determine nutrient dependencies throughout cancer progression-for which a comprehensive characterization remains incomplete. In addition to the widely studied role of genetic alterations driving cancer metabolism, nutrient use in cancer tissue may be affected by several factors including the following: (i) diet, the primary source of bodily nutrients which influences circulating metabolite levels; (ii) tissue of origin, which can influence the tumor's reliance on specific nutrients to support cell metabolism and growth; (iii) local microenvironment, which dictates the accessibility of nutrients to tumor cells; (iv) tumor heterogeneity, which promotes metabolic plasticity and adaptation to nutrient demands; and (v) functional demand, which intensifies metabolic reprogramming to fuel the phenotypic changes required for invasion, growth, or survival. Here, we discuss the influence of these factors on nutrient metabolism and dependence during various steps of tumor development and progression.

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“…While activation of the mTORC1 signaling pathway increased FADS2 expression, inhibition reduced FADS2 expression. Likewise, overexpression of SREBP-1/2 increased FADS2 expression [24]. SREBP-1 and PPARα were both demonstrated to upregulate FADS2 promoter activity in a Luciferase reporter assay [25].…”

Section: Discussionmentioning

confidence: 91%

The Effect of FATP1 on Adipocyte Differentiation in Qinchuan Beef Cattle

Liu

Wang

et al. 2021

Animals

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FATP1 plays an important role in the regulation of fatty acid metabolism and lipid accumulation. In this study, we investigated the patterns of FATP1 expression in various tissues obtained from calf and adult Qinchuan cattle, and in differentiating adipocytes. Next, we investigated the effect of FATP1 expression on preadipocyte differentiation in Qinchuan cattle using overexpression and interference assays. We also identified the differentially expressed genes (DEGs) and pathways associated with FATP1 overexpression/interference. Our results reveal that FATP1 was broadly expressed in heart, kidney, muscle, small intestine, large intestine, and perirenal fat tissues. While FATP1 overexpression promoted preadipocyte differentiation, fat deposition, and the expression of several genes involved in fat metabolism, FATP1 interference had the opposite effects on adipocyte differentiation. Following FATP1 overexpression and FATP1 interference in adipocytes, RNA-seq analysis was performed to identify DEGs related to fat metabolism. The DEGs identified include SLPI, STC1, SEMA6A, TNFRSF19, SLN, PTGS2, ADCYP1, FADS2, and SCD. Pathway analysis revealed that the DEGs were enriched in the PPAR signaling pathway, AMPK signal pathway, and Insulin signaling pathway. Our results provide an in-depth understanding of the function and regulation mechanism of FAPT1 in fat metabolism.

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mTOR Signaling and SREBP Activity Increase FADS2 Expression and Can Activate Sapienate Biosynthesis

Abstract: Highlights d FADS2 expression is prognostic in some cancers d FADS2 is a target of SREBP-1 and SREBP-2 d SREBP activity and mTOR signaling regulate FADS2mediated sapienate metabolism d Torin1 treatment reduces FADS2 expression and sapienate metabolism in xenografts

Cited by 43 publications

References 45 publications

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

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

Nutrient metabolism and cancer in the in vivo context: a metabolic game of give and take

The Effect of FATP1 on Adipocyte Differentiation in Qinchuan Beef Cattle

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