Biosynthesis and Significance of Fatty Acids, Glycerophospholipids, and Triacylglycerol in the Processes of Glioblastoma Tumorigenesis
Abstract
:Simple Summary
Abstract
1. Introduction
2. Synthesis of Fatty Acids and Glioblastoma
2.1. Synthesis of Fatty Acids
2.2. Significance of the Fatty Acid Synthesis Enzymes in Glioblastoma
2.2.1. Fatty Acid Synthase and Acetyl-CoA Carboxylase in Glioblastoma
2.2.2. Elongases in Glioblastoma
2.2.3. Desaturases in Glioblastoma
2.2.4. DHA, EGFR, and Glioblastoma
2.2.5. The Effect of Hypoxia on Fatty Acid Synthesis in Glioblastoma
2.2.6. The Impact of IDH1 Mutation on Fatty Acid Synthesis
3. Synthesis of Glycerophospholipids and Glioblastoma Tumorigenesis
3.1. Glycerol-3-Phosphate Acyltransferases and Glioblastoma Tumorigenesis
3.1.1. Glycerol-3-Phosphate Acyltransferases
3.1.2. Glycerol-3-Phosphate Acyltransferases in Glioblastoma
3.2. Dihydroxyacetone Phosphate Pathway and Glioblastoma Tumorigenesis
3.2.1. Dihydroxyacetone Phosphate Pathway
3.2.2. Dihydroxyacetone Phosphate Pathway in Glioblastoma
3.3. 1-Acylglycerol-3-phosphate O-acyltransferases and Glioblastoma Tumorigenesis
3.3.1. 1-Acylglycerol-3-phosphate O-acyltransferases
3.3.2. 1-Acylglycerol-3-phosphate O-acyltransferases in Glioblastoma
3.4. Synthesis of Glycerophospholipids and Triacylglycerol from Phosphatidic Acid
3.5. Lipins and Glioblastoma Tumorigenesis
3.5.1. Lipins
3.5.2. Lipins in Glioblastoma
3.6. Biosynthesis of Phosphatidylethanolamine and Glioblastoma Tumorigenesis
3.6.1. Biosynthesis of Phosphatidylethanolamine
3.6.2. Biosynthesis of Phosphatidylethanolamine in Glioblastoma
3.7. Biosynthesis of Phosphatidylcholine and Glioblastoma Tumorigenesis
3.7.1. Biosynthesis of Phosphatidylcholine
3.7.2. Biosynthesis of Phosphatidylcholine in Glioblastoma
3.8. Biosynthesis of Phosphatidylserine and Glioblastoma Tumorigenesis
3.8.1. Biosynthesis of Phosphatidylserine
3.8.2. Biosynthesis of Phosphatidylserine in Glioblastoma
3.9. CDP-DAG Synthases and Glioblastoma Tumorigenesis
3.9.1. CDP-DAG Synthases
3.9.2. CDP-DAG Synthases in Glioblastoma
3.10. Biosynthesis of Phosphatidylinositol and Phosphatidylinositol Phosphate and Glioblastoma Tumorigenesis
3.10.1. Biosynthesis of Phosphatidylinositol and Phosphatidylinositol Phosphate
3.10.2. Biosynthesis of Phosphatidylinositol and Phosphatidylinositol Phosphate in Glioblastoma
- Phosphatidylinositol 4-kinase type III, α (PI4KIIIα)/PI4KA;
- Phosphatidylinositol-4-phosphate 5-kinase, type I, β (PIP5KIβ)/PIP5K1B;
- PIP5KIγ/PIP5K1C.
3.11. Biosynthesis of Phosphatidylglycerol and Cardiolipin and Glioblastoma Tumorigenesis
3.11.1. Biosynthesis of Phosphatidylglycerol and Cardiolipin
3.11.2. Biosynthesis of Phosphatidylglycerol and Cardiolipin in Glioblastoma
4. Synthesis of Triacylglycerol and Glioblastoma Tumorigenesis
4.1. Diacylglycerol O-acyltransferases and Glioblastoma Tumorigenesis
4.1.1. Diacylglycerol O-acyltransferases
4.1.2. Diacylglycerol O-acyltransferases in Glioblastoma
4.2. Monoacylglycerol Acyltransferases and Glioblastoma Tumorigenesis
4.2.1. Monoacylglycerol Acyltransferases
4.2.2. Monoacylglycerol Acyltransferases in Glioblastoma
4.3. Lipid Droplets and Triacylglycerol in Glioblastoma
5. Conclusions and Perspective for Future Research
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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Enzyme | Properties | Expression Level in Glioblastoma Tumor Relative to Healthy Brain Tissue | Impact on Survival Rate | Comments | ||
---|---|---|---|---|---|---|
Source | GEPIA [48] | Seifert et al. [49] | Other Data Source | GEPIA [48] | 1. | |
FASN | Synthesis of acyl-CoA to a length of 16 carbons | Expression does not change | Expression does not change | Higher expression in the tumor [12,13,42,43] | No significant impact on prognosis | Expression higher by IDH1 mutation, hypoxia reduces expression, and higher expression in glioblastoma cancer stem cells |
ACC | Production of malonyl-CoA, a substrate for FASN and elongase | Expression does not change | Lower expression in the tumor | No significant impact on prognosis | Hypoxia reduces expression |
Enzyme | Properties | Expression Level in Glioblastoma Tumor Relative to Healthy Brain Tissue | Impact on Survival Rate | Comments | ||
---|---|---|---|---|---|---|
Source | GEPIA [48] | Seifert et al. [49] | Other Data Source | GEPIA [48] | 2. | |
Elovl1 | Elongation of saturated acyl-CoA | Higher expression in the tumor | Expression does not change | Lower expression in the tumor [52] | Worse prognosis | Hypoxia reduces expression |
Elovl2 | Elongation of 20- and 22-carbon polyunsaturated acyl-CoA | Higher expression in the tumor | Expression does not change | Higher expression in the tumor [54]; | No significant impact on prognosis | Higher expression in glioblastoma cancer stem cells |
Expression does not change [52] | ||||||
Elovl3 | Elongation of saturated acyl-CoA | Expression does not change | Expression does not change | Expression does not change [52] | Worse prognosis | Hypoxia reduces expression |
Elovl4 | Elongation of very long-chain fatty acyl-CoA | Expression does not change | Expression does not change | Expression does not change [52] | No significant impact on prognosis | |
Elovl5 | Elongation of 18- and 2-carbon polyunsaturated acyl-CoA | Higher expression in the tumor | Higher expression in the tumor | Expression does not change [52] | No significant impact on prognosis | |
Elovl6 | Elongation of palmitoyl-CoA C16:0 | Expression does not change | Expression does not change | Expression does not change [52] | No significant impact on prognosis | |
Elovl7 | Elongation of saturated acyl-CoA | Lower expression in the tumor | Lower expression in the tumor | Lower expression in the tumor [52] | No significant impact on prognosis | Hypoxia reduces expression |
Enzyme | Properties | Expression Level in the Glioblastoma Tumor Relative to Healthy Brain Tissue | Impact on Survival Rate | Comments | ||
---|---|---|---|---|---|---|
Source | GEPIA [48] | Seifert et al. [49] | Other Data Source | GEPIA [48] | 3. | |
SCD | Desaturation of saturated acyl-CoA, MUFA formation | Expression does not change | Lower expression in the tumor | Lower expression in the tumor [68,69] | No significant impact on prognosis | Hypoxia increases expression; Higher expression in IDH1 mutation |
SCD5 | Desaturation of saturated acyl-CoA, formation of MUFAs | Higher expression in the tumor | Expression does not change | Expression does not change [68] | No significant impact on prognosis | |
FADS1 | Insertion of a double bond into polyunsaturated acyl-CoA | Expression does not change | Expression does not change | Expression does not change [68] | No significant impact on prognosis | Higher expression in glioblastoma cancer stem cells |
FADS2 | Insertion of a double bond into polyunsaturated acyl-CoA | Higher expression in the tumor | Higher expression in the tumor | Lower expression in the tumor [68] | No significant impact on prognosis | Higher expression in glioblastoma cancer stem cells |
FADS3 | Little known | Expression does not change | Expression does not change | Expression does not change [68] | Worse prognosis |
Enzyme | Properties | Expression Level in the Glioblastoma Tumor Relative to Healthy Brain Tissue | Impact on Survival Rate | |
---|---|---|---|---|
Source | GEPIA [48] | Seifert et al. [49] | GEPIA [48] | |
GPAT1 | Mitochondrial enzyme | Expression does not change | Expression does not change | No significant impact on prognosis |
GPAT2 | Mitochondrial enzyme | Expression does not change | No significant impact on prognosis | |
GPAT3 | Enzyme in endoplasmic reticulum, also 1-acylglycerol-3-phosphate O-acyltransferase activity; Questionable GPAT activity; Other name AGPAT10 and AGPAT9 | Expression does not change | Worse prognosis | |
GPAT4 | An enzyme in the endoplasmic reticulum, also 1-acylglycerol-3-phosphate O-acyltransferase activity; Other name AGPAT6 | Higher expression in the tumor | Expression does not change | No significant impact on prognosis |
Enzyme | Properties | Expression Level in the Glioblastoma Tumor Relative to Healthy Brain Tissue | Impact on Survival Rate | |
---|---|---|---|---|
Source | GEPIA [48] | Seifert et al. [49] | GEPIA [48] | |
AGPAT1 | Localization in the endoplasmic reticulum | Expression does not change | Expression does not change | No significant impact on prognosis |
AGPAT2 | Localization in the endoplasmic reticulum | Expression does not change | Expression does not change | No significant impact on prognosis |
AGPAT3 | Localization in the endoplasmic reticulum, lysophospholipids acyltransferase activity | Expression does not change | Lower expression in the tumor | No significant impact on prognosis |
AGPAT4 | Localization in the endoplasmic reticulum | Expression does not change | Lower expression in the tumor | No significant impact on prognosis |
AGPAT5 | Localization in the endoplasmic reticulum and mitochondria, lysophospholipids acyltransferase activity | Higher expression in the tumor | Higher expression in the tumor | No significant impact on prognosis |
AGPAT6 | Localization in the endoplasmic reticulum and on lipid droplets; GPAT activity, also called GPAT4 | Higher expression in the tumor | Expression does not change | No significant impact on prognosis |
AGPAT7 | Localization in the endoplasmic reticulum, Introduces DHA C22:6n-3 into lysophospholipids; Other name LPEAT2 and LPCAT4 | Lower expression in the tumor | Lower expression in the tumor | No significant impact on prognosis |
AGPAT8 | Localization in the endoplasmic reticulum, acyl-CoA:lysocardiolipin acyltransferase activity; Other name ALCAT1 and LCLAT1 | Higher expression in the tumor | Expression does not change | No significant impact on prognosis |
AGPAT9 | Localization in the endoplasmic reticulum and on lipid droplets, lysophospholipids acyltransferase activity, production of dipalmitoylphosphatidylcholine; Other name LPCAT1 | Higher expression in the tumor | Higher expression in the tumor | No significant impact on prognosis |
AGPAT10 | Localization in the endoplasmic reticulum, GPAT activity, also called GPAT3, AGPAT9 | Expression does not change | Worse prognosis | |
AGPAT11 | Localization in the endoplasmic reticulum and on lipid droplets, lysophospholipids acyltransferase activity another name for LPCAT2 | Higher expression in the tumor | Expression does not change | No significant impact on prognosis |
Enzyme | Properties | Expression Level in the Glioblastoma Tumor Relative to Healthy Brain Tissue | Impact on Survival Rate | |
---|---|---|---|---|
Source | GEPIA [48] | Seifert et al. [49] | GEPIA [48] | |
Lipin 1 | Expression increased by hypoxia [115] It interacts with about 30 proteins, including PPARα and PPARγ [116] | Expression does not change | Lower expression in the tumor | No significant impact on prognosis |
Lipin 2 | Reduction in NLRP3 activation, decrease in P2X7 activation [117] | Expression does not change | Expression does not change | No significant impact on prognosis |
Lipin 3 | Expression does not change | Expression does not change | No significant impact on prognosis |
Enzyme | Properties | Expression Level in the Glioblastoma Tumor Relative to Healthy Brain Tissue | Impact on Survival Rate | |
---|---|---|---|---|
Source | GEPIA [48] | Seifert et al. [49] | GEPIA [48] | |
ETNK1 | Production of phosphoethanolamine | Expression does not change | Expression does not change | Better prognosis |
ETNK2 | Generation of phosphoethanolamine, slight choline kinase activity, expression reduced by IDH1 mutation | Expression does not change | Expression does not change | Worse prognosis |
ECT/PCYT2 | Production of CDP-ethanolamine | Expression does not change | Lower expression in the tumor | No significant impact on prognosis |
CEPT1 | Production of PE and PC in Kennedy pathway | Higher expression in the tumor | Expression does not change | Better prognosis (p = 0.062) |
SELENOI | Production of PE and plasmanyl-PE in the Kennedy pathway | Expression does not change | Lower expression in the tumor | No significant impact on prognosis |
PISD/PSD | Production of PE from PS | Expression does not change | Expression does not change | No significant impact on prognosis |
Enzyme | Properties | Expression Level in the Glioblastoma Tumor Relative to Healthy Brain Tissue | Impact on Survival Rate | |
---|---|---|---|---|
Source | GEPIA [48] | Seifert et al. [49] | GEPIA [48] | |
CHKα | Production of phosphocholine, pro-oncogenic properties; Androgen receptor chaperone [149]; Protein kinase activity | Lower expression in the tumor | Expression does not change | No significant impact on prognosis |
CHKβ | Production of phosphocholine | Expression does not change | Expression does not change | No significant impact on prognosis |
CCTα/PCYT1A | Generation of CDP-choline, localization in the endoplasmic reticulum and in the cell nucleus | Expression does not change | Expression does not change | No significant impact on prognosis |
CCTβ/PCYT1B | Generation of CDP-choline, localization in the endoplasmic reticulum | Expression does not change | Expression does not change | No significant impact on prognosis |
CEPT1 | Production of PC and PE in Kennedy pathway | Higher expression in the tumor | Expression does not change | Better prognosis (p = 0.062) |
CHPT1 | Production of PC in Kennedy pathway | Expression does not change | Higher expression in the tumor | No significant impact on prognosis |
PEMT | Production PC from PE | Higher expression in the tumor | Higher expression in the tumor | No significant impact on prognosis |
Enzyme | Properties | Expression Level in the Glioblastoma Tumor Relative to Healthy Brain Tissue | Impact on Survival Rate | |
---|---|---|---|---|
Source | GEPIA [48] | Seifert et al. [49] | GEPIA [48] | |
PTDSS1 | Replacing PC choline with serine, activity is not reduced by PS | Higher expression in the tumor | Lower expression in the tumor | No significant impact on prognosis |
PTDSS2 | Replacing choline in PC and ethanolamine in PE with serine, activity is reduced by PS | Expression does not change | Higher expression in the tumor | Worse prognosis |
Enzyme | Properties | Expression Level in the Glioblastoma Tumor Relative to Healthy Brain Tissue | Impact on Survival Rate | |
---|---|---|---|---|
Source | GEPIA [48] | Seifert et al. [49] | GEPIA [48] | |
CDS1 | An enzyme in the endoplasmic reticulum, PI biosynthesis pathway | Lower expression in the tumor | Lower expression in the tumor | No significant impact on prognosis |
CDS2 | An enzyme in the endoplasmic reticulum, PI biosynthesis pathway | Expression does not change | Expression does not change | Better prognosis |
TAMM41 | Enzyme in the mitochondrion, CL and PG biosynthesis pathway | Expression does not change | Expression does not change | No significant impact on prognosis |
Enzyme | Properties | Expression Level in the Glioblastoma Tumor Relative to Healthy Brain Tissue | Impact on Survival Rate | |
---|---|---|---|---|
Source | GEPIA [48] | Seifert et al. [49] | GEPIA [48] | |
PGPS/PGS1 | Biosynthesis of phosphatidylglycerol phosphate from CDP-DAG and glycerol-3-phosphate | Expression does not change | Expression does not change | No significant impact on prognosis |
PTPMT1 | Generation of phosphatidylglycerol from phosphatidylglycerol phosphate | Higher expression in the tumor | Higher expression in the tumor | No significant impact on prognosis |
CLS1/CRLS1 | Biosynthesis of CL from phosphatidylglycerol and CDP-DAG lysophosphatidylglycerol acyltransferase activity | Higher expression in the tumor | Higher expression in the tumor | No significant impact on prognosis |
Enzyme | Properties | Expression Level in the Glioblastoma Tumor Relative to Healthy Brain Tissue | Impact on Survival Rate | ||
---|---|---|---|---|---|
Source | GEPIA [48] | Seifert et al. [49] | Cheng et al. [135] | ||
DGAT1 | TAG biosynthesis from DAG starvation-induced lipid droplets formation | Expression does not change | Expression does not change | Higher expression in the tumor | Worse prognosis [135] |
No significant impact on prognosis [48] | |||||
DGAT2 | TAG biosynthesis from DAG lipid droplets formation | Expression does not change | Lower expression in the tumor | No significant impact on prognosis [48] |
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Korbecki, J.; Bosiacki, M.; Gutowska, I.; Chlubek, D.; Baranowska-Bosiacka, I. Biosynthesis and Significance of Fatty Acids, Glycerophospholipids, and Triacylglycerol in the Processes of Glioblastoma Tumorigenesis. Cancers 2023, 15, 2183. https://doi.org/10.3390/cancers15072183
Korbecki J, Bosiacki M, Gutowska I, Chlubek D, Baranowska-Bosiacka I. Biosynthesis and Significance of Fatty Acids, Glycerophospholipids, and Triacylglycerol in the Processes of Glioblastoma Tumorigenesis. Cancers. 2023; 15(7):2183. https://doi.org/10.3390/cancers15072183
Chicago/Turabian StyleKorbecki, Jan, Mateusz Bosiacki, Izabela Gutowska, Dariusz Chlubek, and Irena Baranowska-Bosiacka. 2023. "Biosynthesis and Significance of Fatty Acids, Glycerophospholipids, and Triacylglycerol in the Processes of Glioblastoma Tumorigenesis" Cancers 15, no. 7: 2183. https://doi.org/10.3390/cancers15072183