Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA203044 | ENA |
REPOSITORIES: ENA
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Project description:The cholesterol metabolite and SERM, 27HC, is the signaling molecule that links cholesterol to breast cancer pathophysiology Hypercholesterolemia is a risk factor for breast cancer, and patients taking statins demonstrate lower breast cancer incidence and decreased breast cancer recurrence, data that highlights the potential importance of the recent finding that 27-Hydroxycholesterol (27HC), a primary metabolite of cholesterol, acts as a selective estrogen receptor modulator (SERM). The goal of this study was to evaluate the impact of 27HC on breast cancer pathophysiology. Elevation of 27HC in murine models increased tumor growth in an estrogen receptor dependent manner. Importantly, a high cholesterol diet decreased the time to tumor onset and increased tumor growth, and this response required presence of CYP27A1. Within human breast cancer samples, CYP27A1 expression increasesd with grade, in addition to being highly expressed in tumor associated macrophages. Finally 27HC increases metastasis to the lung. The findings herein strongly support a role for 27HC in breast cancer pathophysiology, providing support for the exploration of potential chemopreventative benefits of lower cholesterol diets, and pharmacological inhibitors of HMG-CoA reductase or CYP27A1. MCF-7 cells were treated as indicated in the presence of E2 or vehicle; RNA was isolated and used for preparation of label for 3' expression analysis.
2013-08-01 | E-GEOD-46924 | biostudies-arrayexpress
Project description:The cholesterol metabolite and SERM, 27HC, is the signaling molecule that links cholesterol to breast cancer pathophysiology Hypercholesterolemia is a risk factor for breast cancer, and patients taking statins demonstrate lower breast cancer incidence and decreased breast cancer recurrence, data that highlights the potential importance of the recent finding that 27-Hydroxycholesterol (27HC), a primary metabolite of cholesterol, acts as a selective estrogen receptor modulator (SERM). The goal of this study was to evaluate the impact of 27HC on breast cancer pathophysiology. Elevation of 27HC in murine models increased tumor growth in an estrogen receptor dependent manner. Importantly, a high cholesterol diet decreased the time to tumor onset and increased tumor growth, and this response required presence of CYP27A1. Within human breast cancer samples, CYP27A1 expression increasesd with grade, in addition to being highly expressed in tumor associated macrophages. Finally 27HC increases metastasis to the lung. The findings herein strongly support a role for 27HC in breast cancer pathophysiology, providing support for the exploration of potential chemopreventative benefits of lower cholesterol diets, and pharmacological inhibitors of HMG-CoA reductase or CYP27A1.
2013-08-01 | GSE46924 | GEO
Project description:Small extracellular vesicles (sEVs) are emerging as critical mediators of intercellular communication in the tumor microenvironment. Here, we investigate the mechanisms by which sEVs derived from neutrophils treated with the cholesterol metabolite, 27-hydroxycholesterol (27HC), influence breast cancer progression. sEVs released from 27HC treated neutrophils enhance epithelial-mesenchymal transition (EMT) and stem-like properties in breast cancer cells, resulting in loss of adherence and increased migratory capacity. Decreased miRs within the sEVs resulted in activation of the WNT/ β-catenin signaling pathway in recipient cells and suggest that this may be a predominant pathway for stem-like phenotype and EMT. Our findings underscore a novel mechanism by which 27HC-modulated neutrophils contribute to breast cancer pathophysiology through EV-mediated intercellular communication, suggesting potential therapeutic targets in cancer treatment.
2024-09-03 | GSE272477 | GEO
Project description:Small extracellular vesicles (sEVs) are emerging as critical mediators of intercellular communication in the tumor microenvironment. Here, we investigate the mechanisms by which sEVs derived from neutrophils treated with the cholesterol metabolite, 27-hydroxycholesterol (27HC), influence breast cancer progression. sEVs released from 27HC treated neutrophils enhance epithelial-mesenchymal transition (EMT) and stem-like properties in breast cancer cells, resulting in loss of adherence and increased migratory capacity. Decreased miRs within the sEVs resulted in activation of the WNT/ β-catenin signaling pathway in recipient cells and suggest that this may be a predominant pathway for stem-like phenotype and EMT. Our findings underscore a novel mechanism by which 27HC-modulated neutrophils contribute to breast cancer pathophysiology through EV-mediated intercellular communication, suggesting potential therapeutic targets in cancer treatment.
2024-09-03 | GSE272476 | GEO
Project description:ZMYND8 is a master regulator of 27-hydroxycholesterol metabolism in breast cancer stem cells.
2022-06-02 | GSE203054 | GEO
Project description:ZMYND8 is a master regulator of 27-hydroxycholesterol metabolism in breast cancer stem cells.
2022-06-02 | GSE186543 | GEO
Project description:The cholesterol metabolite 27-hydroxycholesterol increases the secretion of extracellular vesicles which promote breast cancer progression
| PRJNA721435 | ENA
Project description:27 Hydroxycholesterol represses G9a expression via Estrogen Receptor alpha in breast cancer
| PRJNA974381 | ENA
Project description:Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.
| S-EPMC2531291 | biostudies-literature
Project description:RNA extracted at 240min. Samples are rRNA depleted. Expression measurement of Homo sapiens genes.
2019-07-31 | GSE114179 | GEO