Signaling through cholesterol esterification: a new pathway for the cholecystokinin 2 receptor involved in cell growth and invasion

Paillasse, Michaël R.; Médina, Philippe de; Amouroux, Guillaume; Mhamdi, Loubna; Poirot, Marc; Silvente-Poirot, Sandrine

doi:10.1194/jlr.m800668-jlr200

Cited by 62 publications

(55 citation statements)

References 49 publications

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“…Also exosomes were shown to carry the PPAR nuclear receptor modulator 15d-PGJ2 [9]. PPAR regulates cholesterol homeostasis, and cholesterol ester have been shown to trigger cell proliferation [31]. Cholesterol biosynthesis involves enzymes organized at the site of the Anti Estrogen Binding Site (AEBS).…”

Section: Sorting Lipids In Exosomes (Figure 2)mentioning

confidence: 99%

Exosomes as intercellular signalosomes and pharmacological effectors

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Subra

Silvente-Poirot

et al. 2011

Biochemical Pharmacology

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International audienceCell secretion is a general process involved in various biological responses. Exosomes are part of this process and have gained considerable scientific interest in the past five years. Several steps through investigations across the last 20years can explain this interest. First characterized during reticulocyte maturation, they were next characterized as a key player in the immune response and cancer immunotherapy. More recently they were characterized as vectors of mRNAs, miRNAs and also lipid mediators able to act on target cells. They are the only type of vesicles released from an intracellular compartment from cells in viable conditions. They appear as a vectorized signaling system operating from inside a donor cell towards either the periphery, the cytosol, or possibly to the nucleus of target cells. Exosomes from normal cells trigger positive effects, whereas those from pathological ones, such as tumor cells or infected ones may trigger non-positive health effects. Therefore regulating the biogenesis and secretion of exosomes appear as a pharmacological challenge to intervene in various pathophysiologies. Exosome biogenesis and molecular content, interaction with target cells, utilisation as biomarkers, and functional effects in various pathophysiologies are considered in this review

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Section: Sorting Lipids In Exosomes (Figure 2)mentioning

confidence: 99%

Exosomes as intercellular signalosomes and pharmacological effectors

Record

Subra

Silvente-Poirot

et al. 2011

Biochemical Pharmacology

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483

336

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“…SW-620, MDA-MB-231, E151A, and MCF-7 cells were plated on six-well plates (40,000 cells/well). ACAT activity in intact cells was measured as described previously (Paillasse et al, 2009). Cells were preincubated for 15 min with solvent vehicle or increasing concentrations of auraptene or Sah 58-035 ranging from 0.1 to 100 M in complete medium.…”

Section: Chemicalsmentioning

confidence: 99%

“…14 C]Cholesterol (0.2 Ci/well) was added, and the cells were incubated for 24 h. At the end of the incubation, intracellular and secreted lipids in the supernatant were extracted and then separated by TLC as described previously (Paillasse et al, 2009). Free and esterified cholesterol were identified using purified 14 C commercial standards, and the radioactivity of each individual lipid was quantified using a phosphor screen (Storm; GE Healthcare).…”

Section: Chemicalsmentioning

confidence: 99%

“…We have reported that Tam inhibited the Acyl-CoA:Cholesterol Acyl Transferase (ACAT) activity in macrophages and tumor cell lines de Medina et al, 2004de Medina et al, , 2006Payré et al, 2008). It is noteworthy that cholesteryl esters have been reported to accumulate in tumors and to be involved in cell proliferation and invasiveness that are blocked by the inhibition of ACAT (Tosi and Tugnoli, 2005;Paillasse et al, 2009). The AEBS is a hetero-oligomeric proteinaceous binding site made up of multifunctional enzymes involved in cholesterol metabolism (Kedjouar et al, 2004) that include cholesterol-5,6-epoxide hydrolase activity (ChEH) (de Medina et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

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Auraptene Is an Inhibitor of Cholesterol Esterification and a Modulator of Estrogen Receptors

Médina¹,

Genovese²,

Paillasse³

et al. 2010

Mol Pharmacol

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Auraptene is a prenyloxycoumarin from Citrus species with chemopreventive properties against colitis-related colon and breast cancers through a yet-undefined mechanism. To decipher its mechanism of action, we used a ligand-structure based approach. We established that auraptene fits with a pharmacophore involved in both the inhibition of acyl-CoA:cholesterol acyl transferase (ACAT) and the modulation of estrogen receptors (ERs). We confirmed experimentally that auraptene inhibits ACAT and binds to ERs in a concentration-dependent manner and that it inhibited ACAT in rat liver microsomes and in intact cancer cells of murine and human origins, with an IC 50 value in the micromolar range. Auraptene bound to ERs with affinities of 7.8 M for ER␣ and 7.9 M for ER␤, stabilized ERs, and modulated their transcriptional activity via an ER-dependent reporter gene and endogenous genes. We further established that these effects correlated well with the control of growth and invasiveness of tumor cells. Our data shed light on the molecular mechanism underlying the anticancer and chemopreventive effects of auraptene.

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“…We and others have proposed that accumulation of CE spares energy needed for de novo sterol synthesis, allowing greater proliferation and migration and perhaps a quicker return to growth after a period of stasis (Batetta, Pani et al 1999;Antalis, Arnold et al 2010;Antalis, Uchida et al 2011). The process of cholesterol esterification was linked to proliferation in multiple studies in different cancer cell lines (Batetta, Pani et al 1999;Peiretti, Dessi et al 2007;Paillasse, de Medina et al 2009;Antalis, Arnold et al 2010;Mulas, Abete et al 2011), implying a complex network of signaling pathways and gene expression that ties cholesterol accretion to tumorigenesis. However, the exact role of CE in tumorigenesis remains to be determined.…”

Section: Experimental and Mechanistic Evidence For Role Of Ldl In Cancermentioning

confidence: 99%