Cellular Fatty Acid Metabolism and Cancer

Currie, Erin; Schulze, Almut; Zechner, Rudolf; Walther, Tobias C.; Farese, Robert V.

doi:10.1016/j.cmet.2013.05.017

Cited by 1,670 publications

(1,567 citation statements)

References 76 publications

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“…Rapid cell proliferation requires increased uptake of lipids and de novo lipogenesis to continuously provide mevalonate pathway metabolites, cholesterol, and fatty acids needed for cell membrane synthesis, cell signaling, post-translational modifications of proteins, and energy supply (12,49). Increased SREBP signaling in bone marrow and peripheral blood cells of patients with MDS has been associated with poor survival prognosis (50).…”

Section: -Azacytidine Restricts Srebp Activationmentioning

confidence: 99%

The Epigenetic Drug 5-Azacytidine Interferes with Cholesterol and Lipid Metabolism

Poirier

Samami

Mamarbachi

et al. 2014

Journal of Biological Chemistry

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Background:The anticancer drug 5-azacytidine acts through an incompletely understood mechanism. Results: 5-Azacytidine reprograms the glycerolipid biosynthesis pathway and prevents activation of master transcription factors that regulate lipid homeostasis. Conclusion: 5-Azacytidine deeply modifies how cells manage cholesterol and lipid synthesis. Significance: The findings unravel important insights into the mechanism of 5-azacytidine and highlight new potential cancer therapeutics.

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Section: -Azacytidine Restricts Srebp Activationmentioning

confidence: 99%

The Epigenetic Drug 5-Azacytidine Interferes with Cholesterol and Lipid Metabolism

Poirier

Samami

Mamarbachi

et al. 2014

Journal of Biological Chemistry

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“…Specifically, increased de novo lipogenesis is frequently observed in tumor cells. [20][21][22] De novo lipogenesis is the synthesis of endogenous fatty acids from acetyl-CoA. 23 It is a highly-coordinated process, which involved several lipogenic enzymes (Fig.…”

Section: De Novo Lipogenesis In Cancermentioning

confidence: 99%

Oncogene dependent requirement of fatty acid synthase in hepatocellular carcinoma

et al. 2017

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Hepatocellular carcinoma (HCC), the most frequent primary tumor of the liver, is an aggressive cancer type with limited treatment options. Cumulating evidence underlines a crucial role of aberrant lipid biosynthesis (a process known as de novo lipogenesis) along carcinogenesis. Previous studies showed that suppression of fatty acid synthase (FASN), the major enzyme responsible for de novo lipogenesis, is highly detrimental for the in vitro growth of HCC cell lines. To assess whether de novo lipogenesis is required for liver carcinogenesis, we have generated various mouse models of liver cancer by stably overexpressing candidate oncogenes in the mouse liver via hydrodynamic gene delivery. We found that overexpression of FASN in the mouse liver is unable to malignantly transform hepatocytes. However, genetic deletion of FASN totally suppresses hepatocarcinogenesis driven by AKT and AKT/c-Met protooncogenes in mice. On the other hand, liver tumor development is completely unaffected by FASN depletion in mice coexpressing b-catenin and c-Met. Our data indicate that tumors might be either addicted to or independent from de novo lipogenesis for their growth depending on the oncogenes involved. Additional investigation is required to unravel the molecular mechanisms whereby some oncogenes render cancer cells resistant to inhibition of de novo lipogenesis.

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“…FA is transported to mitochondria by carnitine palmitoyl transferase 1 (CPT1) and catabolized to acetyl-CoA by β-oxidation. Acetyl-CoA is utilized to fuel the TCA cycle to produce ATP [36]. Ex vivo treatment of mouse HSCs with the CPT1 inhibitor etomoxir induces repopulation defects following HSC transplantation [37].…”

Section: Adipocytes Fatty Acid Metabolism and Hematopoiesismentioning

confidence: 99%

Metabolic regulation of hematopoietic and leukemic stem/progenitor cells under homeostatic and stress conditions

Karigane

Takubo

2017

Int J Hematol

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organisms. HSPCs are composed of hematopoietic stem cells (HSCs) and several types of lineage-biased, but not fully committed, hematopoietic progenitor cells (HPCs). HSC capacities such as self-renewal and multilineage differentiation maintain the whole hematopoietic system over an organism's lifetime [1], and contribute to blood regeneration under stress condition, whereas HPCs reportedly function to maintain the supply of blood cells at steady state [2,3]. The surrounding BM microenvironment or "niche" determines HSC fate, namely its quiescence, symmetric/asymmetric division, differentiation, or migration potential, in both steady state and during stress. It is now evident that metabolic programs operating in HSCs play critical roles in maintaining hematopoietic homeostasis [4], often in response to BM niche signals [5]. Cellular pathways generate various metabolites through enzymatic activity that supplies material used as fuel, building blocks for other factors, or modulators of intra-or intercellular activities (Fig. 1). Despite the fact that numerous biochemical studies have addressed HSC metabolic regulation, numerous gaps in our knowledge of that regulation remain.Recently, novel means to fractionate metabolites using highly sensitive mass spectrometric technology [6] have dramatically facilitated metabolome analysis. These technologies reduce the need for high cell numbers and increase sensitivity of metabolite selection. As a result, metabolome analysis is feasible in rare cell populations such as HSCs. These analyses have revealed that metabolic programs play critical roles in maintaining stem cell "stemness" (Fig. 2). Here we review recent advances in the field of how metabolic changes regulate HSC dynamics under quiescence, proliferation, and differentiation from the viewpoint of each pathway. In addition to the normal HSC system, we also review activity of leukemia-related metabolic pathways, tumor-associated metabolites (oncometabolites), and Abstract Hematopoietic stem cells (HSCs) exhibit multilineage differentiation and self-renewal activities that maintain the entire hematopoietic system during an organism's lifetime. These abilities are sustained by intrinsic transcriptional programs and extrinsic cues from the microenvironment or niche. Recent studies using metabolomics technologies reveal that metabolic regulation plays an essential role in HSC maintenance. Metabolic pathways provide energy and building blocks for other factors functioning at steady state and in stress. Here we review recent advances in our understanding of metabolic regulation in HSCs relevant to cell cycle quiescence, symmetric/asymmetric division, and proliferation following stress and lineage commitment, and discuss the therapeutic potential of targeting metabolic factors or pathways to treat hematological malignancies.

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Cellular Fatty Acid Metabolism and Cancer

Cited by 1,670 publications

References 76 publications

The Epigenetic Drug 5-Azacytidine Interferes with Cholesterol and Lipid Metabolism

The Epigenetic Drug 5-Azacytidine Interferes with Cholesterol and Lipid Metabolism

Oncogene dependent requirement of fatty acid synthase in hepatocellular carcinoma

Metabolic regulation of hematopoietic and leukemic stem/progenitor cells under homeostatic and stress conditions

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