Key Molecules of Fatty Acid Metabolism in Gastric Cancer
Abstract
1. Introduction
2. Functions of Fatty Acids
3. Key Molecules in Fatty Acid Metabolism
3.1. Key Molecules in the Endogenous Synthesis of FAs
3.1.1. Sterol Regulatory Element-Binding Protein 1 (SREBP1)
3.1.2. ACLY
3.1.3. Acetyl-CoA Synthases (ACSs)
3.1.4. ACC
3.1.5. FASN
3.1.6. SCD1
3.2. Key Molecules for Exogenous Uptake of FAs
3.2.1. CD36
3.2.2. FABPs
3.3. A Key Molecule in Fatty Acid Catabolism
Carnitine palmitoyltransferase 1 (CPT1)
4. Concluding Remarks
Author Contributions
Funding
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Molecules | Expression | Findings | Influence |
---|---|---|---|
SREBP1 | Upregulate [24,25] | Activation of SREBP-1c in GC resulted in upregulation of SCD and FASN and downregulation of ELOVL6. Knockdown of SREBP1c significantly inhibited the proliferation, invasiveness, and migration of GC cells [25] | Tumor promotion [25] |
ACLY | Upregulate [33] | Inhibition of ACLY by high-dose sodium citrate reduced the growth of GC in mice [37] | Poor prognosis [33] Tumor promotion [37] |
ACSS3 | - | ACSS3 knockdown could suppress colony formation under a regular culture, inhibit wound-healing ability under starvation conditions, and increase the basal level of cell death, even more dramatically under starvation conditions [42] | Poor prognosis [42] Tumor promotion [42] |
ACSL4 | Downregulate [46] | ACSL4 knockdown enhanced cell growth, colony formation, and cell migration in vitro and promoted subcutaneous xenografts’ growth in vivo [46] | Tumor suppressing [46] |
ACSL5 | - | SiRNA-mediated repression of ACSL5 inhibits the oncogenicity of MKN01 cells [47] | Tumor promotion [47] |
pACC | Downregulate [53] | Metformin-induced pACC upregulation resulted in significant inhibition of GC cell proliferation and colony formation [51] | Poor prognosis [51,53] Tumor promotion [51] |
FASN | Upregulate [24,58,59,60,62] | The FASN inhibitor C75 or siFASN blocked endogenous fatty acid metabolism in GC and attenuated MACC1 upregulation-induced cell proliferation and chemo-resistance to oxaliplatin to varying degrees [63] | Poor prognosis [59,61] Tumor promotion [60,63] Oxaliplatin resistance [63] |
Inhibition of FASN also inhibited GC proliferation and metastasis by targeting the mTOR/Gli1 signaling pathway [60] | |||
SCD1 | Upregulate [70,71] | SCD1 regulates cell stemness through the Hippo/YAP pathway, which influences gastric carcinogenesis, chemo-resistance, and metastasis [70] | Oxaliplatin resistance [70] Tumor promotion [70,71,72] |
SCD1 promotes the proliferative capacity, migratory capacity, and stemness of GC cells, and SCD1 also has an anti-iron death effect and accelerates the growth of transplanted tumors in mice [71] | |||
The mean tumor volume in the A939572-treated group was reduced by nearly 50% relative to vehicle-treated animals [72] | |||
CD36 | Upregulate [77] | CD36 mediates c-Myc-induced DEK transcription in GC cells, then upregulation of DEK enhances GSK-3β/β-catenin signaling [78] | Poor prognosis [78] Tumor promotion [78,80,81] |
Palmitic acid promoted GC metastasis through phosphorylation of AKT and CD36 promoted GC metastasis as a key mediator of AKT/GSK-3β/β-catenin signaling [81] | |||
FABP4 | Downregulate [96] Upregulate [97] | Regulation of FABP4 by a small-molecule FABP4 inhibitor or siFABP4 restores primary cilia to inhibit the proliferation and migration of GCs, thus exhibiting potential anticancer effects [94] | Tumor promotion [94] Poor prognosis [94,96] |
FABP5 | Upregulate [97] | Silencing of the FABP5 gene attenuated the invasiveness of GC cells, prevented cell proliferation, and stalled the cell cycle in the G0/G1 phase, leading to a significant increase in apoptosis [95,99] | Tumor promotion [95,97,98,99,101] |
PA enters GC cells, promotes the nuclear transport of FABP5, which then increases the GC nuclear protein levels of SP1 and PA-induced GC metastasis via FABP5/SP1/UCA1 signaling, contributing efficient prevention and therapeutic strategies for GC [100] | |||
CPT1 | Upregulate [106,107] | CPT1A overexpression activates fatty acid oxidation in GC cells by increasing the NADP/NADPH ratio and thus increases the proliferation, invasion, and epithelial–mesenchymal transition (EMT) of GC cells [106] | Poor prognosis [106,111] Enhanced tumorigenesis [106,108,110] |
CPT1A succinylates LDHA on K222, which thereby reduces the binding and inhibits the degradation of LDHA and promotes GC invasion and proliferation [108] | |||
The CPT1 inhibitor perhexiline and oxaliplatin synergistically inhibit tumor xenograft progression, suggesting that CPT1-mediated fatty acid translocation and further fatty acid oxidation may be associated with oxaliplatin resistance [110] |
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Li, C.; Zhang, L.; Qiu, Z.; Deng, W.; Wang, W. Key Molecules of Fatty Acid Metabolism in Gastric Cancer. Biomolecules 2022, 12, 706. https://doi.org/10.3390/biom12050706
Li C, Zhang L, Qiu Z, Deng W, Wang W. Key Molecules of Fatty Acid Metabolism in Gastric Cancer. Biomolecules. 2022; 12(5):706. https://doi.org/10.3390/biom12050706
Chicago/Turabian StyleLi, Chunlei, Lilong Zhang, Zhendong Qiu, Wenhong Deng, and Weixing Wang. 2022. "Key Molecules of Fatty Acid Metabolism in Gastric Cancer" Biomolecules 12, no. 5: 706. https://doi.org/10.3390/biom12050706
APA StyleLi, C., Zhang, L., Qiu, Z., Deng, W., & Wang, W. (2022). Key Molecules of Fatty Acid Metabolism in Gastric Cancer. Biomolecules, 12(5), 706. https://doi.org/10.3390/biom12050706