Deregulation of sphingolipid and glycosphingolipid metabolism in colorectal cancer

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00027162%3A_____%2F23%3AN0000208" target="_blank" >RIV/00027162:_____/23:N0000208 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Deregulation of sphingolipid and glycosphingolipid metabolism in colorectal cancer

Popis výsledku v původním jazyce

Poster. In: FEBS Special Meeting 2023: Sphingolipid Biology, Funchal, Madeira Island, Portugal, October 8 -13, 2023, p. 110. Colorectal cancer (CRC) development is associated with metabolic reprogramming leading to alterations in lipid metabolism and lipidmediated signaling. A detailed HPLC/MS/MS description of changes in sphingolipidome may help to discriminate between normal and CRC tissues. We identified two major clusters of changes in sphingolipid (SL) and glycosphingolipid (GSL) metabolism: 1. upregulation of SLs (sphingosine, sphingosine1phosphate, ceramide1phosphate, lysosphingomyelin and lysosphingosine); 2. increased levels of a series of GSLs in tumor samples; the most prominent was the accumulation of lactosylceramide (LacCer) levels; glucosylceramide (GlcCer), GM3, GM1a, GD2, GA2, and, to lesser extent, of GD3 and Gb3 were also significantly increased, as compared with normal adjacent tissues. Gene expression of CERS2, CERS6, ASAH1 and SPHK1 as well as the genes of fatty acid metabolism FASN and PLA2G10 was increased in accordance with SL concentrations in tumor samples. LacCer synthases B4GALT5 and especially B4GALT6, GOLPH3 (which may induce enzymatic activities of GSL synthases) and GlcCer transporter FAPP2 were upregulated in tumor tissue. However, a majority of genes of GSL metabolism were downregulated, including UGCG, GBA2 and several GSL synthases. We hypothesize that increased metabolic flux of fatty acids (and possibly also glucose) may partly contribute to increased biosynthesis of SLs and GlcCer, respectively. Upregulation of LacCer synthases leading to LacCer accumulation might contribute to increased levels of GSLs in tumor tissues, which could be further potentiated via upregulation of GOLPH3 and FAPP2. Together, our data suggest that, apart from the previously reported increase in S1P/ceramide ratio, increased levels of LacCer may represent another major alteration of sphingolipid metabolism that is associated with CRC progression.

Název v anglickém jazyce

Deregulation of sphingolipid and glycosphingolipid metabolism in colorectal cancer

Popis výsledku anglicky

Poster. In: FEBS Special Meeting 2023: Sphingolipid Biology, Funchal, Madeira Island, Portugal, October 8 -13, 2023, p. 110. Colorectal cancer (CRC) development is associated with metabolic reprogramming leading to alterations in lipid metabolism and lipidmediated signaling. A detailed HPLC/MS/MS description of changes in sphingolipidome may help to discriminate between normal and CRC tissues. We identified two major clusters of changes in sphingolipid (SL) and glycosphingolipid (GSL) metabolism: 1. upregulation of SLs (sphingosine, sphingosine1phosphate, ceramide1phosphate, lysosphingomyelin and lysosphingosine); 2. increased levels of a series of GSLs in tumor samples; the most prominent was the accumulation of lactosylceramide (LacCer) levels; glucosylceramide (GlcCer), GM3, GM1a, GD2, GA2, and, to lesser extent, of GD3 and Gb3 were also significantly increased, as compared with normal adjacent tissues. Gene expression of CERS2, CERS6, ASAH1 and SPHK1 as well as the genes of fatty acid metabolism FASN and PLA2G10 was increased in accordance with SL concentrations in tumor samples. LacCer synthases B4GALT5 and especially B4GALT6, GOLPH3 (which may induce enzymatic activities of GSL synthases) and GlcCer transporter FAPP2 were upregulated in tumor tissue. However, a majority of genes of GSL metabolism were downregulated, including UGCG, GBA2 and several GSL synthases. We hypothesize that increased metabolic flux of fatty acids (and possibly also glucose) may partly contribute to increased biosynthesis of SLs and GlcCer, respectively. Upregulation of LacCer synthases leading to LacCer accumulation might contribute to increased levels of GSLs in tumor tissues, which could be further potentiated via upregulation of GOLPH3 and FAPP2. Together, our data suggest that, apart from the previously reported increase in S1P/ceramide ratio, increased levels of LacCer may represent another major alteration of sphingolipid metabolism that is associated with CRC progression.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

30108 - Toxicology

Projekt

<a href="/cs/project/NU21-03-00421" target="_blank" >NU21-03-00421: Glykosfingolipidy a jejich metabolické dráhy jako potenciální biomarkery nádorů tlustého střeva</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2023

Kód důvěrnosti údajů

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