60+ Reviews Take You To Learn About Fatty Acids In Cancer

Fatty Acids in Cancer 1.
Overview Lipid metabolism, especially the synthesis of fatty acids (FAs), is an important cellular process that converts nutrients into metabolic intermediates for membrane biosynthesis, energy storage, and signaling molecules.
produce
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Altered lipid metabolism is an important metabolic phenotype of cancer cells
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Therefore, blocking lipid supply in cancer cells can have a major impact on cancer cell bioenergetics, membrane biosynthesis, and intracellular signaling processes
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In addition, alterations in lipid availability also affect cancer cell migration, induction of angiogenesis, metabolic symbiosis, evasion of immune surveillance, and drug resistance in cancer
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FA synthesis has received considerable attention as a potential target for cancer therapy, but strategies targeting this process have not yet been translated into clinical practice (Ref: 27658529; IF: 60.
7)
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Fatty acid synthesis major events in cancer II.
The role of fatty acids in the tumor microenvironment Although there is abundant evidence that tumors undergo de novo FA synthesis, it is unclear whether this phenotype is driven solely by cancer cell-intrinsic processes or is also regulated by environmental conditions
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Studies have shown that adding palmitate or oleate can completely restore the viability of cancer cells after inhibition of FASN4
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Therefore, cancer cells should be able to use exogenous lipids when precursors are restricted or FA synthesis is blocked
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The tumor microenvironment is often hypoxic
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Under hypoxic conditions, the entry of glucose-derived pyruvate into the TCA cycle is inhibited
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Therefore, cells must switch to alternative carbon sources to generate acetyl-CoA for FA synthesis Flexibility in the FA synthesis process in the tumor microenvironment 3.
Function of fatty acids in cancer cells Given the complex role of lipids in cellular physiology, it is clear , dysregulated FA synthesis must lead to cancer at many levels, including not only the production of building blocks for membrane synthesis during cell growth or the provision of substrates for ATP synthesis (BOX 1 ) and the regulation of signaling pathways involved in cell proliferation and survival
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1.
FA synthesis and cell growth Actively proliferating tissues require FA to synthesize structural lipids
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Therefore, the induction of lipid synthesis must go hand in hand with cell growth, which is a prerequisite for cell division
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Inhibition of FA synthesis, for example by inhibiting ACLY with small molecules, impairs the growth of immortalized hematopoietic cells in response to growth factor stimulation
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2.
Cardiolipin altering FA synthesis and modification can also affect the function of intracellular organelles in membrane-containing cells by changing the composition of specific membrane lipids
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Cardiolipins (CLs) are structurally unique phospholipids primarily located in the inner mitochondrial membrane, where they control mitochondrial respiration and serve as signaling platforms during the induction of apoptosis (Figure a)
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3.
The abundance and saturation of FA in protein acylation cells also determine the activity of signaling proteins that require acylation function
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An example is the WNT protein, which is frequently dysregulated in human cancers
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Since aberrant activation of the WNT-β-catenin pathway promotes the loss of intercellular adhesion and disrupts epithelial cell polarity, modulation of FA desaturation may promote cancer progression and metastasis (lower panel b)
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4.
Lipid mediators Lipids can also act as important signaling molecules
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These include the bioactive lipids sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA), which are autocrine and paracrine via G protein-coupled LPA receptors (LPAR) on the plasma membrane of cancer, immune and endothelial cells Signals and stimulates proliferation, migration, inflammation, and angiogenesis (panel c)
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Lipids contribute to cancer cell signaling processes 4.
The role of fatty acids in cancer progression In addition to supporting tumorigenesis, lipids are involved in a variety of cellular processes that are critical for cellular transformation, tumor development, and disease progression.
leading cause of cancer-related death
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Tumor Initiation Bioenergetics • Lipids provide substrates for energy production • Lipids can be used for energy storage and promote metabolic membrane synthesis after reoxygenation • Fatty acids (FA) are substrates for phosphoglyceride and sphingolipid synthesis during cell growth • Membrane lipids support organelle function (eg mitochondria) • Activity of signaling molecules requires lipid modifications (eg, acylation of WNTs and prenylation of RHOs) • Lipid mediators as a second secondary pathway for autocrine receptor signaling Messengers or ligands (eg, phosphatidylinositol 3,4,5-triphosphate (PIP3; also known as PtdIns(3,4,5)P3) and lysophosphatidic acid (LPA)) tumor progression and drug resistance • Biophysical properties of structural lipids alter membrane fluidity • Prostaglandin E2 (PGE2) induction by transforming growth factor-beta to induce epithelial-mesenchymal transition • Small GTPases angiogenic prenylation via the mevalonate pathway • PGE2 secreted by cancer cells induces vascular growth • Free fatty acids induce vascular endothelial growth factor (VEGF) expression by binding and activating peroxisome proliferator-activated receptor-γ (PPARγ) immunosuppression • PGE2 induces macrophage repopulation Programmed to the M2 isoform • Release of PGE2 blocks type 1 interferon-dependent innate immune responses • Secretion of linoleic acid leads to loss of T helper cells • Metabolic competition between cancer cells and immune cells limits immune cell function Metabolic symbiosis • Cancer cells induce lipolysis in adipocytes to obtain substrates for energy production • Lipids may be involved in metabolite exchange between different cell populations Drug resistance • Lipid composition of mitochondrial membranes determines cancer cell chemosensitivity • Increased saturation of membrane lipids Tolerance to oxidative stress Fatty acid synthesis inhibitors in preclinical and clinical development 5.
Additional evidence that fatty acids are associated with cancer 1.
Most tumors have abnormally activated lipid metabolism that enables them to synthesize , extending and desaturating fatty acids to support proliferation (Ref: 30728499; IF: 49); 2.
PMN-MDSCs (polymorphonuclear myeloid-derived suppressor cells) are pathologically activated neutrophils that are critical for regulating cancer immune responses Importantly, (Ref: 30996346; IF: 49) studies found that selective pharmacological inhibition of FATP2 abolished the activity of PMN-MDSCs and significantly delayed tumor progression in mice
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Represents that FATP2 can selectively inhibit the function of PMN-MDSCs and improve the efficiency of cancer therapy
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3.
Cancer metabolism can be viewed as a network of pathways with plasticity, feedback loops, and crosstalk to ensure the adaptability of tumor cells, and its plasticity is the key
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Studies (Ref: 23446547; IF: 60) found that FAO (fatty acid oxidation) may provide this by generating ATP and NADPH when needed, eliminating potentially toxic lipids, inhibiting pro-apoptotic pathways and providing metabolic intermediates for cell growth.
kind of plasticity
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The role of fatty acid oxidation in the metabolism, growth and survival of cancer cells 4.
Cachexia is a devastating muscle wasting syndrome
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It is most common in patients with advanced cancer and is one of the leading causes of cancer-related morbidity and mortality
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Metabolomic analysis of the study (Ref: 27135739; IF: 59) showed that factors secreted by cachexia cancer cells rapidly induce excessive fatty acid oxidation in human myotubes, leading to oxidative stress, p38 activation and impaired muscle growth
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Therefore, cancer-induced cachexia can be prevented by targeting fatty acid-induced oxidative stress
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5.
Uniquely, a study (Ref: 26950360; IF: 53) targeting metabolomic methods in triple-negative breast cancer found that TNBC overexpressing MYC showed increased bioenergy dependence on FAO, and inhibiting FAO could increase the bioenergy dependence of FAO.
as a potential treatment strategy for TNBC (below)
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6.
This is very powerful.
Fatty acids are associated with star hotspots: ferroptosis ferroptosis is an iron-dependent regulatory necrosis mediated by lipid peroxidation
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Cancer cells survive through stressful conditions of altered lipid metabolism
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A study published in December 2020 (Ref: 33288688; IF: 11) found that the expressions of very long-chain fatty acid protein 5 (ELOVL5) and fatty acid desaturase 1 (FADS1) were significantly up-regulated in mesenchymal gastric cancer cells (GCs).
Causes ferroptosis sensitization
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The unsaturated fatty acid (PUFA) biosynthetic pathway plays an important role in ferroptosis
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A study (Ref: 32652074) published in Development Cell (IF: 12) Aug 20 found that DGLA (a fatty acid named dihomogamma-linolenic acid) can induce iron in animal models and actual human cancer cells Death.
At this point, do you have a certain understanding of the function and research direction of fatty acids? If you have no clue, you can see how others do simple fatty acid research
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References 1.
The multifaceted roles of fatty acid synthesis in cancer 2.
Cancer metabolism: fatty acid oxidation in the limelight Global view of human protein fatty-acid pathways and functions 3.
Dietary Lipids Induce Ferroptosis in Caenorhabditiselegans and Human Cancer Cells 4.
Polyunsaturated fatty acid biosynthesis pathway determines ferroptosis sensitivity in gastric cancer