Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA398637 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Lipid addiction via Fatty Acid Synthase activates PI3K signaling in B cell non-Hodgkin’s Lymphoma (bNHL)
| PRJNA398632 | ENA
Project description:Lipid addiction via Fatty Acid Synthase activates PI3K signaling in B cell non-Hodgkin’s Lymphoma (bNHL) [Affymetrix]
| PRJNA398628 | ENA
Project description:Lipid addiction via Fatty Acid Synthase activates PI3K signaling in B cell non-Hodgkin’s Lymphoma (bNHL) [SUDHL2, SUHDL10, and Raji]
| PRJNA399104 | ENA
Project description:Dysregulated lipid metabolism is an oncogenic mechanism that leads to increased de novo fatty acid biosynthesis via elevated expression of fatty acid synthase (FASN) in cancer. FASN catalyzes biosynthesis of (C16) palmitic acid by using Acetyl CoA, malonyl CoA and NADPH as substrates. Palmitic acid and its derivatives participate as signaling lipids andinvolved in the regulation of receptor functions associated with many biological processes. and furtherThis includes contribute formation of cell structures, and all these processes which are essential for both normal and malignant cell growth and proliferation. In this study, we investigated the biological impact of FASN inhibition in B cell Non Hodgkin Lymphoma (bNHL) cells using FASN inhibitors Cerulenin and other novel agents (TVB3166, TVB3567). Inhibition of FASN resulted in a dose dependent increase in cell death and apoptosis in the bNHL and primary tumor cells. Transcriptomic and comprehensive systems biology analysis of cerulenin, TVB3166 or TVB3567 treated bNHL cells revealed conserved activation of (TNF) immune and PI3K signaling, and inhibition of cell cycle pathways as prominent responses to FASN inhibition. Cell fractionation and western blot analysis of cCerulenin treated cells showed translocation of TNF receptor adaptor proteins (TRAF2 and RIP), docking of AKT and PI3K/p110 subunits to cell membrane and activation of PI3K/AKT pathways by phosphorylation in SUDHL2 and SUDHL4 bNHL cells, while these mechanisms were constitutively active in cerulenin treated SUDHL10 bNHL cells. Disruption of lipid raft formation by methyl β cyclodextrin inhibited PI3K signaling and downregulated FASN expression in SUDHL10 cells. Subsequently, we observed that combination of FASN (cerulenin) and PI3K (Buparlisib) inhibitors resulted in synergistic cell death in bNHL cell lines and increased apoptosis accompanied with down-regulation of FASN expression in bNHL cell lines and primary cells, implicating the importance of PI3K in the regulation of lipid metabolism. Further mass spectrometric evaluation of cerulenin and Buparlisib treated DLBCL cells fed with C14C glucose, synergistically decreased the biosynthesis of palmitic acid and its derivatives compared to single agent treatments. Our conclusions from these investigations suggest that simultaneous blocking of PI3K and FASN is likely to exert stronger inhibition of lipid metabolism and enhance cell death in lymphoma.
2018-02-01 | GSE102764 | GEO
Project description:Dysregulated lipid metabolism is an oncogenic mechanism that leads to increased de novo fatty acid biosynthesis via elevated expression of fatty acid synthase (FASN) in cancer. FASN catalyzes biosynthesis of (C16) palmitic acid by using Acetyl CoA, malonyl CoA and NADPH as substrates. Palmitic acid and its derivatives participate as signaling lipids andinvolved in the regulation of receptor functions associated with many biological processes. and furtherThis includes contribute formation of cell structures, and all these processes which are essential for both normal and malignant cell growth and proliferation. In this study, we investigated the biological impact of FASN inhibition in B cell Non Hodgkin Lymphoma (bNHL) cells using FASN inhibitors Cerulenin and other novel agents (TVB3166, TVB3567). Inhibition of FASN resulted in a dose dependent increase in cell death and apoptosis in the bNHL and primary tumor cells. Transcriptomic and comprehensive systems biology analysis of cerulenin, TVB3166 or TVB3567 treated bNHL cells revealed conserved activation of (TNF) immune and PI3K signaling, and inhibition of cell cycle pathways as prominent responses to FASN inhibition. Cell fractionation and western blot analysis of cCerulenin treated cells showed translocation of TNF receptor adaptor proteins (TRAF2 and RIP), docking of AKT and PI3K/p110 subunits to cell membrane and activation of PI3K/AKT pathways by phosphorylation in SUDHL2 and SUDHL4 bNHL cells, while these mechanisms were constitutively active in cerulenin treated SUDHL10 bNHL cells. Disruption of lipid raft formation by methyl β cyclodextrin inhibited PI3K signaling and downregulated FASN expression in SUDHL10 cells. Subsequently, we observed that combination of FASN (cerulenin) and PI3K (Buparlisib) inhibitors resulted in synergistic cell death in bNHL cell lines and increased apoptosis accompanied with down-regulation of FASN expression in bNHL cell lines and primary cells, implicating the importance of PI3K in the regulation of lipid metabolism. Further mass spectrometric evaluation of cerulenin and Buparlisib treated DLBCL cells fed with C14C glucose, synergistically decreased the biosynthesis of palmitic acid and its derivatives compared to single agent treatments. Our conclusions from these investigations suggest that simultaneous blocking of PI3K and FASN is likely to exert stronger inhibition of lipid metabolism and enhance cell death in lymphoma.
2018-02-01 | GSE102760 | GEO
Project description:Dysregulated lipid metabolism is an oncogenic mechanism that leads to increased de novo fatty acid biosynthesis via elevated expression of fatty acid synthase (FASN) in cancer. FASN catalyzes biosynthesis of (C16) palmitic acid by using Acetyl CoA, malonyl CoA and NADPH as substrates. Palmitic acid and its derivatives participate as signaling lipids andinvolved in the regulation of receptor functions associated with many biological processes. and furtherThis includes contribute formation of cell structures, and all these processes which are essential for both normal and malignant cell growth and proliferation. In this study, we investigated the biological impact of FASN inhibition in B cell Non Hodgkin Lymphoma (bNHL) cells using FASN inhibitors Cerulenin and other novel agents (TVB3166, TVB3567). Inhibition of FASN resulted in a dose dependent increase in cell death and apoptosis in the bNHL and primary tumor cells. Transcriptomic and comprehensive systems biology analysis of cerulenin, TVB3166 or TVB3567 treated bNHL cells revealed conserved activation of (TNF) immune and PI3K signaling, and inhibition of cell cycle pathways as prominent responses to FASN inhibition. Cell fractionation and western blot analysis of cCerulenin treated cells showed translocation of TNF receptor adaptor proteins (TRAF2 and RIP), docking of AKT and PI3K/p110 subunits to cell membrane and activation of PI3K/AKT pathways by phosphorylation in SUDHL2 and SUDHL4 bNHL cells, while these mechanisms were constitutively active in cerulenin treated SUDHL10 bNHL cells. Disruption of lipid raft formation by methyl β cyclodextrin inhibited PI3K signaling and downregulated FASN expression in SUDHL10 cells. Subsequently, we observed that combination of FASN (cerulenin) and PI3K (Buparlisib) inhibitors resulted in synergistic cell death in bNHL cell lines and increased apoptosis accompanied with down-regulation of FASN expression in bNHL cell lines and primary cells, implicating the importance of PI3K in the regulation of lipid metabolism. Further mass spectrometric evaluation of cerulenin and Buparlisib treated DLBCL cells fed with C14C glucose, synergistically decreased the biosynthesis of palmitic acid and its derivatives compared to single agent treatments. Our conclusions from these investigations suggest that simultaneous blocking of PI3K and FASN is likely to exert stronger inhibition of lipid metabolism and enhance cell death in lymphoma.
2018-02-01 | GSE102791 | GEO
Project description:Fatty acid synthase is a major enzyme involved in de novo lipogenesis, associated with energy homeostasis, lipid storage and signalling in normal liver cells. The effect of fatty acid synthase knockdown in normal liver cells (THLE 2) using siRNA mediated gene silencing were assesed for global gene deregulations. The deregulated metabolism, cell signalling and cell cycle pathway related gene expressions were analysed. Statistical significance values were also recorded. This expermental analysis clearly points to a important biochemical role for FASN in normal liver cell physiology. Total RNA was extracted from the THLE 2 cells transfected with FASN siRNA at 48h, along with its untransfected control cells. cDNA converted samples were run on microarray platform- Illumina HumanHT-12 V4.0 expression beadchip
2016-06-02 | E-GEOD-82096 | biostudies-arrayexpress
Project description:Essential fatty acids (FA) are not only energy-rich molecules; they are also an important component of the membrane bilayer and recently have been implicated in induction of fatty acid synthase (FAS) and other genes. Using gene chip analysis, we have found that arachidonic acid (AA), an omega-6 fatty acid, induced 11 genes that are regulated by NFkappaB. We verified gene induction by omega-6 fatty acids including COX2, IKBA, NFKB, GMCSF, IL1B, CXCL1, TNFA, IL6, LTA, IL8, PPARG, and ICAM1 using qRTPCR. PGE2 synthesis was increased within 5min of addition of AA. Analysis of upstream signal transduction showed that within 5min of FA addition, phophatidylinositol 3-kinase (PI3K) was significantly activated followed by activation of Akt at 30min. ERK1 and 2, p38, and SAPK/JNK were not phosphorylated after omega-6 FA addition. Thirty minutes after FA addition, we found a significant 3-fold increase in translocation of NFkappaB transcription factor to the nucleus. Addition of non-steroidal anti-inflammatory drug (NSAID) caused a decrease in cox-2 protein synthesis, PGE2 synthesis as well as inhibition of PI3K activation. We have previously shown that AA induced proliferation is also blocked (P<0.001) by PI3K inhibitor LY294002. LY294002 also significantly inhibited the AA induced gene expression of COX2, IL1B, GMCSF, and ICAM1. Taken together, the data suggests that AA via conversion to PGE2 plays an important role in stimulation of growth related genes and proliferation via PI3K signaling and NFkappaB translocation to the nucleus.
2007-07-03 | E-GEOD-3737 | biostudies-arrayexpress
Project description:Thraustochytrids of the genera Schizochytrium and Aurantiochytrium accumulate oils rich in the essential, marine n3 fatty acid docosahexaenoic acid (DHA). DHA production in Aurantiochytrium sp T66 was studied with the aim to provide more knowledge about factors that affect the DHA-productivities and the contributions of the two enzyme systems used for fatty acid synthesis in thraustochytrids, fatty acid synthetase (FAS) and PUFA-synthase. Fermentations with nitrogen starvation, which is well-known to initiate lipid accumulation in oleaginous organisms, were compared to fermentations with nitrogen in excess where lipid accumulation was obtained by oxygen limitation. The specific productivities of fatty acids originating from FAS were considerably higher under nitrogen starvation than with nitrogen in excess, while the specific productivities of DHA were the same at both conditions. Global transcriptome analysis showed significant up-regulation of FAS under N-deficient conditions, while the PUFA-synthase genes were only marginally upregulated. Neither of them was upregulated under O2-limitation where nitrogen was in excess, suggesting that N-starvation mainly affects the FAS and may be less important for the PUFA-synthase. The transcriptome analysis also revealed responses likely to be related to the generation of reducing power (NADPH) for fatty acid synthesis.
2019-12-19 | GSE134374 | GEO
Project description:Fatty acid synthase is a major enzyme involved in de novo lipogenesis, associated with energy homeostasis, lipid storage and signalling in normal liver cells. The effect of fatty acid synthase knockdown in normal liver cells (THLE 2) using siRNA mediated gene silencing were assesed for global gene deregulations. The deregulated metabolism, cell signalling and cell cycle pathway related gene expressions were analysed. Statistical significance values were also recorded. This expermental analysis clearly points to a important biochemical role for FASN in normal liver cell physiology.
2016-06-02 | GSE82096 | GEO