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, Maria Francesca; Lappano, Rosamaria; Marco, Paola De; Pupo, Marco; Vivacqua, Adele; Sisci, Diego; Abonante, Sergio; Iacopetta, Domenico; Cappello, Anna Rita; Dolce, Vincenza; Maggiolini, Marcello

doi:10.1074/jbc.m112.417303

Cited by 93 publications

(83 citation statements)

References 59 publications

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“…33 Estrogens also upregulate the FASN gene by ERK activation and a similar effect has been observed in activated Jurkat cells. 34,35 Activated T cells undergo some metabolic changes common to tumor cells and this may represent a general metabolic reprogramming during cell growth and proliferation.…”

mentioning

confidence: 73%

Metal oxide nanoparticles interact with immune cells and activate different cellular responses

Simón‐Vázquez¹,

Lozano‐Fernández²,

Dávila-Grana³

et al. 2016

IJN

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Besides cell death, nanoparticles (Nps) can induce other cellular responses such as inflammation. The potential immune response mediated by the exposure of human lymphoid cells to metal oxide Nps (moNps) was characterized using four different moNps (CeO 2 , TiO 2 , Al 2 O 3 , and ZnO) to study the three most relevant mitogen-activated protein kinase subfamilies and the nuclear factor kappa-light-chain-enhancer of the activated B-cell inhibitor, IκBα, as well as the expression of several genes by immune cells incubated with these Nps. The moNps activated different signaling pathways and altered the gene expression in human lymphocyte cells. The ZnO Nps were the most active and the release of Zn 2+ ions was the main mechanism of toxicity. CeO 2 Nps induced the smallest changes in gene expression and in the IκBα protein. The effects of the particles were strongly dependent on the type and concentration of the Nps and on the cell activation status prior to Np exposure.

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mentioning

confidence: 73%

Metal oxide nanoparticles interact with immune cells and activate different cellular responses

Simón‐Vázquez¹,

Lozano‐Fernández²,

Dávila-Grana³

et al. 2016

IJN

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“…18 We found that in both population samples, the hypofunctional GPER P16L variant was associated with increased LDL concentrations in women, following a recessive model. Furthermore, in cellular studies, we demonstrate that G1 agonist activation of GPER in HepG2 cells, which endogenously express GPER, 19,20 leads to reduced PCSK9 expression and increased LDL receptor expression. Overall, these studies support an important role of GPER in regulation of plasma lipoprotein metabolism.…”

mentioning

confidence: 99%

G-Protein Estrogen Receptor as a Regulator of Low-Density Lipoprotein Cholesterol Metabolism

Hussain

Ding

Connelly

et al. 2015

ATVB

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T he importance of estrogen as a regulator of plasma lipid metabolism has been most clearly demonstrated in settings of estrogen deficiency (eg, menopause). Bilateral ovariectomy in premenopausal women causes an increase in plasma levels of low-density lipoprotein (LDL) when compared with premenopausal women with preserved ovaries.1 Furthermore, LDL cholesterol levels increase after onset of menopause. 2Multiple mechanisms have been proposed by which estrogens regulate lipoprotein metabolism in humans, including induction of hepatic LDL receptor expression, 3,4 reduction of hepatic secretion of acyl-coenzyme A: cholesterol acyltransferase 2-derived cholesteryl esters in plasma lipoproteins, 5 reduction of hepatic lipase, 6 and reduction of levels of proprotein convertase subtilisin kexin type 9 (PCSK9), 7 a key regulator of LDL receptor metabolism. 8 The receptor(s) mediating estrogen's effects on LDL metabolism is unclear. Estrogen's effects are triggered via 2 main receptor types. Classic estrogen receptors (ERs) have been shown to have both nuclear and cytoplasmic/membraneassociated sites of effect.9,10 More recently, a G-proteincoupled receptor, G-protein ER (GPER; aka GPR30) has been shown to mediate some of the so-called rapid (nongenomic) effects of estrogen. 11 We have recently shown that GPER is also activated by aldosterone. Objective-Estrogen deficiency is linked with increased low-density lipoprotein (LDL) cholesterol. The hormone receptor mediating this effect is unknown. G-protein estrogen receptor (GPER) is a recently recognized G-protein-coupled receptor that is activated by estrogens. We recently identified a common hypofunctional missense variant of GPER, namely P16L. However, the role of GPER in LDL metabolism is unknown. Therefore, we examined the association of the P16L genotype with plasma LDL cholesterol level. Furthermore, we studied the role of GPER in regulating expression of the LDL receptor and proprotein convertase subtilisin kexin type 9. Approach and Results-Our discovery cohort was a genetically isolated population of Northern European descent, and our validation cohort consisted of normal, healthy women aged 18 to 56 years from London, Ontario. In addition, we examined the effect of GPER on the regulation of proprotein convertase subtilisin kexin type 9 and LDL receptor expression by the treatment with the GPER agonist, G1. In the discovery cohort, GPER P16L genotype was associated with a significant increase in LDL cholesterol (mean±SEM): 3.18±0.05, 3.25±0.08, and 4.25±0.33 mmol/L, respectively, in subjects with CC (homozygous for P16), CT (heterozygotes), and TT (homozygous for L16) genotypes (P<0.05). In the validation cohort (n=339), the GPER P16L genotype was associated with a similar increase in LDL cholesterol: 2.17±0.05, 2.34±0.06, and 2.42±0.16 mmol/L, respectively, in subjects with CC, CT, and TT genotypes (P<0.05). In the human hepatic carcinoma cell line, the GPER agonist, G1, mediated a concentration-dependent increase in LDL receptor expression, blocked by eith...

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“…GPER/ GPR30 activation has been shown to transactivate EGFR via the release of the membrane-tethered HB-EGF and subsequent activation of MAPK (37,38). This mechanism was shown to be responsible for a number of genomic effects of GPER/GPR30 activation, such as up-regulating the expression of c-fos, cyclin A and D1, and fatty acid synthase (5)(6)(7)(8). We hypothesized that a similar mechanism could account for the effects of GPER/ GPR30 to up-regulate CaM expression at the transcriptional level.…”

Section: Gper/gpr30 Up-regulates Cam Mrna Via Transactivation Of Egfrmentioning

confidence: 99%

“…Estrogen also has rapid actions not fully explained by activities of ER␣ or ER␤, such as intracellular Ca 2ϩ mobilization, cAMP production, and phosphorylation. The G protein-coupled estrogen receptor 1 (GPER/GPR30) is associated with many rapid, pregenomic effects of estrogen (3,4) and also genomic effects, including up-regulation of genes like c-fos (5) and cyclin A and D1 (6,7), and fatty acid synthase (8). Since its recognition as a GPCR sensitive to estrogen (9,10), GPER/GPR30 has received significant attention (4).…”

Section: Estrogen Exerts Many Effects On the Vascular Endothelium Camentioning

confidence: 99%

Estrogen Enhances Linkage in the Vascular Endothelial Calmodulin Network via a Feedforward Mechanism at the G Protein-coupled Estrogen Receptor 1

Tran

Firkins

Giles

et al. 2016

Journal of Biological Chemistry

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

Cited by 93 publications

References 59 publications

Metal oxide nanoparticles interact with immune cells and activate different cellular responses

Metal oxide nanoparticles interact with immune cells and activate different cellular responses

G-Protein Estrogen Receptor as a Regulator of Low-Density Lipoprotein Cholesterol Metabolism

Estrogen Enhances Linkage in the Vascular Endothelial Calmodulin Network via a Feedforward Mechanism at the G Protein-coupled Estrogen Receptor 1

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