The Lipogenesis Pathway as a Cancer Target

Abramson, H. N.

doi:10.1021/jm2005805

Cited by 136 publications

(116 citation statements)

References 184 publications

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“…In MCF-7 breast cancer cells, FASN expression was influenced by E2 and progestins through the sterol receptor element binding protein 1 (SREBP-1) pathway as also observed in prostate cancer cells by androgens (52). In these studies, the activation of steroid receptors mediated the up-regulation of FASN as the antiandrogen bicalutamide, the antiprogestin mifepristone (RU486), and the antiestrogens 4-hydroxytamoxifen and faslodex (ICI 182780) inhibited the FASN response to the cognate ligands of hormone receptors (30,36,(53)(54)(55)(56). Nevertheless, the inhibition of MAPK and PI3K signaling pathways abolished FASN induction by steroids (32,51), suggesting that complex transduction mechanisms may contribute to the regulation of FASN expression.…”

Section: Discussionmentioning

confidence: 99%

G Protein-coupled Estrogen Receptor Mediates the Up-regulation of Fatty Acid Synthase Induced by 17β-Estradiol in Cancer Cells and Cancer-associated Fibroblasts

Santolla

Lappano

Marco

et al. 2012

Journal of Biological Chemistry

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Background: Fatty acid synthase (FASN) is a key lipogenic enzyme regulated by various factors, including estrogens. Results: GPER mediates FASN expression and activity induced by estrogens in cancer cells. Conclusion: Fatty acid biogenesis is regulated by estrogens through GPER. Significance: GPER may be included among the transduction mediators involved by estrogens in regulating FASN expression and activity.

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Section: Discussionmentioning

confidence: 99%

G Protein-coupled Estrogen Receptor Mediates the Up-regulation of Fatty Acid Synthase Induced by 17β-Estradiol in Cancer Cells and Cancer-associated Fibroblasts

Santolla

Lappano

Marco

et al. 2012

Journal of Biological Chemistry

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“…These analogues included (þ) and (À)-2,2-difluorocitrate, both of which showed activity against rat liver ACLY (30). In addition to the synthetic inhibitors, a naturally occurring citrate analog, namely (À)-hydroxycitrate, was found to be a potent inhibitor of ACLY (30). Treatment with (À)-hydroxycitrate results in decreased cholesterol and fatty acid synthesis in HepG2 cells.…”

Section: Acly Inhibition For Cancer Therapeuticsmentioning

confidence: 99%

“…Treatment with (À)-hydroxycitrate results in decreased cholesterol and fatty acid synthesis in HepG2 cells. However, this inhibitor has certain limitations; for example, it is inefficiently transported across the cell membrane, and very high concentrations are required to achieve complete inhibition of ACLY activity (30). Moreover, (À)-hydroxycitrate inhibits IDH at concentrations that are similar to those required to inhibit ACLY.…”

Section: Acly Inhibition For Cancer Therapeuticsmentioning

confidence: 99%

ATP-Citrate Lyase: A Key Player in Cancer Metabolism

2012

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ATP-citrate lyase (ACLY) is a cytosolic enzyme that catalyzes the generation of acetyl CoA from citrate. Acetyl CoA is a vital building block for the endogenous biosynthesis of fatty acids and cholesterol and is involved in isoprenoid-based protein modifications. Acetyl CoA is also required for acetylation reactions that modify proteins, such as histone acetylation. ACLY is upregulated or activated in several types of cancers, and its inhibition is known to induce proliferation arrest in cancer cells both in vitro and in vivo. The present review highlights current knowledge about the role of ACLY in cancer cells, with special reference to the different pathways that are linked by ACLY. Cancer Res; 72(15);

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“…However, numerous studies have confi rmed that neoplastic tissues show aberrant activation of de novo lipogenesis ( 29 ). In fact, overexpression of lipogenic enzymes is reported as a common characteristic of many cancers ( 27,30,31 ), and inhibition of different enzymes within the FA biosynthetic pathway can block cancer cell growth ( 28,32,33 ). FAs can be converted to triacylglycerols (TAGs) for storage and to phospholipids for membrane biogenesis.…”

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confidence: 99%

Microtargeting cancer metabolism: opening new therapeutic windows based on lipid metabolism

Cedrón

Molina

2016

Journal of Lipid Research

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and fl exibility to adapt to the microenvironment (oxygen, pH, and nutrient availability) ( 2-4 ).MicroRNAs are small single-stranded noncoding RNAs (19-25 nucleotides) that posttranscriptionally repress the expression of mRNAs implicated in nearly all cellular processes, such as cell cycle, apoptosis, autophagy, stemness, differentiation, angiogenesis, infl ammation, drug resistance, stress response, transformation, and migration. MicroRNAs are frequently deregulated in cancer and so they are important biomarkers for diagnosis and prognosis of the cellular outcome ( 5,6 ) Importantly, individual microRNAs, combinations of microRNAs, or even artifi cial microRNAs can specifi cally be designed to affect entire biological pathways ( 7,8 ), and this makes them good candidates for therapeutic intervention compared with classical single target approaches.In this review, we briefl y describe the altered cancer cell metabolism, and then we discuss the use of microRNAs as modulators of specifi c metabolic pathways in cancer (summarized in Fig. 1 ). We note the promising potentiallity of microRNAs for therapeutic intervention toward the altered lipid metabolism in cancer (summarized in Fig. 2 ). In an attempt to open new therapeutic windows, we emphasize two exciting scenarios for microRNA-mediated intervention that need to be further explored: 1 ) the cooperation between FA biosynthesis (lipogenesis) and FA oxidation (FAO) as a survival mechanism in cancer; and 2 ) the regulation of the intracellular lipid content in the Abstract Metabolic reprogramming has emerged as a hallmark of cancer. MicroRNAs are noncoding RNAs that posttranscriptionally repress the expression of target mRNAs implicated in multiple physiological processes, including apoptosis, differentiation, and cancer. MicroRNAs can affect entire biological pathways, making them good candidates for therapeutic intervention compared with classical single target approaches. Moreover, microRNAs may become more relevant in the fi ne-tuning adaptation to stress situations, such as oncogenic events, hypoxia, nutrient deprivation, and oxidative stress. Furthermore, artifi cial microRNAs can be designed to modulate the expression of multiple targets of a specifi c pathway. In this review, we describe the metabolic reprogramming associated to cancer, with a special interest in the altered lipid metabolism. Next, we describe specifi c features of microRNAs that make them relevant to target cancer cell metabolism. Finally, in an attempt to open new therapeutic windows, we emphasize two exciting scenarios for microRNA-mediated intervention that need to be further explored: 1 ) the cooperation between FA biosynthesis (lipogenesis) and FA oxidation as complementary partners for the survival of cancer cells; and 2 ) the regulation of the intracellular lipid content modulating both lipid storage into lipid droplets, and lipid mobilization through lipolysis and/or lipophagy. metabolism is interrupted, they may rely on glucose-dependent anaplerosis of the TCA cycle ( 11 ). This...

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The Lipogenesis Pathway as a Cancer Target

Cited by 136 publications

References 184 publications

G Protein-coupled Estrogen Receptor Mediates the Up-regulation of Fatty Acid Synthase Induced by 17β-Estradiol in Cancer Cells and Cancer-associated Fibroblasts

G Protein-coupled Estrogen Receptor Mediates the Up-regulation of Fatty Acid Synthase Induced by 17β-Estradiol in Cancer Cells and Cancer-associated Fibroblasts

ATP-Citrate Lyase: A Key Player in Cancer Metabolism

Microtargeting cancer metabolism: opening new therapeutic windows based on lipid metabolism

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