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Lipid metabolism, apoptosis and cancer therapy.

Huang C, Freter C - Int J Mol Sci (2015)

Bottom Line: These bioactive lipid molecules known as signaling molecules, such as fatty acid, eicosanoids, diacylglycerol, phosphatidic acid, lysophophatidic acid, ceramide, sphingosine, sphingosine-1-phosphate, phosphatidylinositol-3 phosphate, and cholesterol, are involved in the activation or regulation of different signaling pathways.Lipid metabolism participates in the regulation of many cellular processes such as cell growth, proliferation, differentiation, survival, apoptosis, inflammation, motility, membrane homeostasis, chemotherapy response, and drug resistance.Bioactive lipid molecules promote apoptosis via the intrinsic pathway by modulating mitochondrial membrane permeability and activating different enzymes including caspases.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology/Oncology, Department of Internal Medicine, School of Medicine and Cancer Center, Saint Louis University, 3655 Vista Avenue, Saint Louis, MO 63110, USA. chunfahuang@slu.edu.

ABSTRACT
Lipid metabolism is regulated by multiple signaling pathways, and generates a variety of bioactive lipid molecules. These bioactive lipid molecules known as signaling molecules, such as fatty acid, eicosanoids, diacylglycerol, phosphatidic acid, lysophophatidic acid, ceramide, sphingosine, sphingosine-1-phosphate, phosphatidylinositol-3 phosphate, and cholesterol, are involved in the activation or regulation of different signaling pathways. Lipid metabolism participates in the regulation of many cellular processes such as cell growth, proliferation, differentiation, survival, apoptosis, inflammation, motility, membrane homeostasis, chemotherapy response, and drug resistance. Bioactive lipid molecules promote apoptosis via the intrinsic pathway by modulating mitochondrial membrane permeability and activating different enzymes including caspases. In this review, we discuss recent data in the fields of lipid metabolism, lipid-mediated apoptosis, and cancer therapy. In conclusion, understanding the underlying molecular mechanism of lipid metabolism and the function of different lipid molecules could provide the basis for cancer cell death rationale, discover novel and potential targets, and develop new anticancer drugs for cancer therapy.

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Related in: MedlinePlus

Signaling transduction in lipid metabolism. Extracellular signals induce different pathways that regulate lipid metabolism in the cells. Protein kinases include protein kinase A, B and C; mitogen-activated protein kinases (MAPK) includes extracellular signal-regulated kinases (ERK), p38 kinase and c-Jun N-terminal kinases (JNK); Enzymes that are involved in lipid uptake, transport, synthesis and degradation; Ions: Ca2+, K+, Na+, H+. Some bioactive lipid molecules are ligands, and in turn induce different signaling pathways. MS, mechanical stress.
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ijms-16-00924-f003: Signaling transduction in lipid metabolism. Extracellular signals induce different pathways that regulate lipid metabolism in the cells. Protein kinases include protein kinase A, B and C; mitogen-activated protein kinases (MAPK) includes extracellular signal-regulated kinases (ERK), p38 kinase and c-Jun N-terminal kinases (JNK); Enzymes that are involved in lipid uptake, transport, synthesis and degradation; Ions: Ca2+, K+, Na+, H+. Some bioactive lipid molecules are ligands, and in turn induce different signaling pathways. MS, mechanical stress.

Mentions: Lipid metabolism, including lipid uptake, transport, synthesis, and degradation, is a complex process. Biosynthesis and degradation of different lipids are regulated by different signaling pathways, and the same lipid can be regulated by different signaling pathways in different tissues and cells as well as under physiological, pathophysiological or therapeutic conditions [1,2]. Either activation or inhibition of these signaling pathways is based on cell needs and responds to environmental changes (Figure 3). There are more than one hundred enzymes regulating lipid metabolism in the cells. Recent studies show that expression of many of these enzymes is regulated by microRNA (miRNA). It indicates that miRNA also plays an important role in lipid metabolism. Alteration of lipid metabolism leads to the changes of membrane compositions, protein distribution and function, gene expression, and cellular functions, and further causes the development and progression of many diseases such as inflammation, hypertension, diabetes, liver disease, heart disease, renal disease, neurological disorder, cystic fibrosis, and cancer [3,23]. On the other hand, manipulation of lipid metabolism can lead cancer cells to apoptosis.


Lipid metabolism, apoptosis and cancer therapy.

Huang C, Freter C - Int J Mol Sci (2015)

Signaling transduction in lipid metabolism. Extracellular signals induce different pathways that regulate lipid metabolism in the cells. Protein kinases include protein kinase A, B and C; mitogen-activated protein kinases (MAPK) includes extracellular signal-regulated kinases (ERK), p38 kinase and c-Jun N-terminal kinases (JNK); Enzymes that are involved in lipid uptake, transport, synthesis and degradation; Ions: Ca2+, K+, Na+, H+. Some bioactive lipid molecules are ligands, and in turn induce different signaling pathways. MS, mechanical stress.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4307283&req=5

ijms-16-00924-f003: Signaling transduction in lipid metabolism. Extracellular signals induce different pathways that regulate lipid metabolism in the cells. Protein kinases include protein kinase A, B and C; mitogen-activated protein kinases (MAPK) includes extracellular signal-regulated kinases (ERK), p38 kinase and c-Jun N-terminal kinases (JNK); Enzymes that are involved in lipid uptake, transport, synthesis and degradation; Ions: Ca2+, K+, Na+, H+. Some bioactive lipid molecules are ligands, and in turn induce different signaling pathways. MS, mechanical stress.
Mentions: Lipid metabolism, including lipid uptake, transport, synthesis, and degradation, is a complex process. Biosynthesis and degradation of different lipids are regulated by different signaling pathways, and the same lipid can be regulated by different signaling pathways in different tissues and cells as well as under physiological, pathophysiological or therapeutic conditions [1,2]. Either activation or inhibition of these signaling pathways is based on cell needs and responds to environmental changes (Figure 3). There are more than one hundred enzymes regulating lipid metabolism in the cells. Recent studies show that expression of many of these enzymes is regulated by microRNA (miRNA). It indicates that miRNA also plays an important role in lipid metabolism. Alteration of lipid metabolism leads to the changes of membrane compositions, protein distribution and function, gene expression, and cellular functions, and further causes the development and progression of many diseases such as inflammation, hypertension, diabetes, liver disease, heart disease, renal disease, neurological disorder, cystic fibrosis, and cancer [3,23]. On the other hand, manipulation of lipid metabolism can lead cancer cells to apoptosis.

Bottom Line: These bioactive lipid molecules known as signaling molecules, such as fatty acid, eicosanoids, diacylglycerol, phosphatidic acid, lysophophatidic acid, ceramide, sphingosine, sphingosine-1-phosphate, phosphatidylinositol-3 phosphate, and cholesterol, are involved in the activation or regulation of different signaling pathways.Lipid metabolism participates in the regulation of many cellular processes such as cell growth, proliferation, differentiation, survival, apoptosis, inflammation, motility, membrane homeostasis, chemotherapy response, and drug resistance.Bioactive lipid molecules promote apoptosis via the intrinsic pathway by modulating mitochondrial membrane permeability and activating different enzymes including caspases.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology/Oncology, Department of Internal Medicine, School of Medicine and Cancer Center, Saint Louis University, 3655 Vista Avenue, Saint Louis, MO 63110, USA. chunfahuang@slu.edu.

ABSTRACT
Lipid metabolism is regulated by multiple signaling pathways, and generates a variety of bioactive lipid molecules. These bioactive lipid molecules known as signaling molecules, such as fatty acid, eicosanoids, diacylglycerol, phosphatidic acid, lysophophatidic acid, ceramide, sphingosine, sphingosine-1-phosphate, phosphatidylinositol-3 phosphate, and cholesterol, are involved in the activation or regulation of different signaling pathways. Lipid metabolism participates in the regulation of many cellular processes such as cell growth, proliferation, differentiation, survival, apoptosis, inflammation, motility, membrane homeostasis, chemotherapy response, and drug resistance. Bioactive lipid molecules promote apoptosis via the intrinsic pathway by modulating mitochondrial membrane permeability and activating different enzymes including caspases. In this review, we discuss recent data in the fields of lipid metabolism, lipid-mediated apoptosis, and cancer therapy. In conclusion, understanding the underlying molecular mechanism of lipid metabolism and the function of different lipid molecules could provide the basis for cancer cell death rationale, discover novel and potential targets, and develop new anticancer drugs for cancer therapy.

Show MeSH
Related in: MedlinePlus