Abstract
Metabolic activity of malignant cells is very different from that of their nontransformed equivalents, which establishes metabolic reprogramming as an important hallmark of every transformed cell. In particular, the current arena of research in this field aims to understand the regulatory effect of oncogenic signaling on metabolic rewiring in transformed cells in order to exploit this for therapeutic benefit. Alterations in lipid metabolism are one of the main aspects of metabolic rewiring of transformed cells. Up-regulation of several lipogenic enzymes has been reported to be a characteristic of various cancer types. Lysophosphatidic acid (LPA), a simple byproduct of the lipid biosynthesis pathway, has gained immense importance due to its elevated level in several cancers and associated growth-promoting activity. Importantly, a current study revealed its role in increased de novo lipid synthesis through up-regulation of sterol regulatory element-binding protein 1, a master regulator of lipid metabolism. This review summarizes the recent insights in the field of oncolipid LPA-mediated signaling in regard to lipid metabolism in cancers. Future work in this domain is required to understand the up-regulation of the de novo synthesis pathway and the role of its end products in malignant cells. This will open a new arena of research toward the development of specific metabolic inhibitors that can add to the pre-existing chemotherapeutics in order to increase the efficacy of clinical output in cancer patients.
Keywords:
cancer; lipid metabolism; lysophosphatidic acid; metabolic reprogramming.
© 2017 Federation of European Biochemical Societies.
MeSH terms
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Animals
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Antineoplastic Agents / pharmacology
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Antineoplastic Agents / therapeutic use
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Antineoplastic Combined Chemotherapy Protocols / pharmacology
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use
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Drugs, Investigational / pharmacology
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Drugs, Investigational / therapeutic use
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Fatty Acid Synthase, Type I / antagonists & inhibitors
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Fatty Acid Synthase, Type I / metabolism
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Gene Expression Regulation, Neoplastic / drug effects
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Humans
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Lipid Metabolism* / drug effects
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Lipids / antagonists & inhibitors*
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Lipids / blood
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Lipogenesis / drug effects
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Lysophospholipids / antagonists & inhibitors*
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Lysophospholipids / blood
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Lysophospholipids / metabolism
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Models, Biological*
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Molecular Targeted Therapy
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Neoplasm Proteins / agonists
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Neoplasm Proteins / antagonists & inhibitors
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism
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Neoplasms / blood
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Neoplasms / drug therapy
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Neoplasms / metabolism*
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Neoplasms / pathology
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Phosphoric Diester Hydrolases / chemistry
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Phosphoric Diester Hydrolases / genetics
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Phosphoric Diester Hydrolases / metabolism
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Receptors, Lysophosphatidic Acid / antagonists & inhibitors
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Receptors, Lysophosphatidic Acid / genetics
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Receptors, Lysophosphatidic Acid / metabolism
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Signal Transduction* / drug effects
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Stearoyl-CoA Desaturase / antagonists & inhibitors
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Stearoyl-CoA Desaturase / genetics
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Stearoyl-CoA Desaturase / metabolism
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Sterol Regulatory Element Binding Protein 1 / agonists
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Sterol Regulatory Element Binding Protein 1 / genetics
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Sterol Regulatory Element Binding Protein 1 / metabolism
Substances
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Antineoplastic Agents
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Drugs, Investigational
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Lipids
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Lysophospholipids
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Neoplasm Proteins
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Receptors, Lysophosphatidic Acid
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SREBF1 protein, human
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Sterol Regulatory Element Binding Protein 1
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oncolipids
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SCD1 protein, human
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Stearoyl-CoA Desaturase
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FASN protein, human
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Fatty Acid Synthase, Type I
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Phosphoric Diester Hydrolases
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alkylglycerophosphoethanolamine phosphodiesterase
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lysophosphatidic acid