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The ERRalpha metabolic nuclear receptor controls growth of colon cancer cells

ABSTRACT: Estrogen-Related Receptor alpha (ERRα) is a nuclear receptor that acts principally as a regulator of metabolism processes particularly in tissues subjected to high-energy demand. Besides its implication in energy metabolism and mitochondrial biogenesis, ERRα was recently associated with tumorigenesis. Notably, increased expression of ERRα was noted in different cancerous tissues as breast, ovary and colon. However, supplemental studies are required to better understand the role of ERRα in colon carcinoma. We used microarrays to detail gene expression during ERRalpha knockdown in HCT116 cells and identified distinct classes of up and down-regulated genes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE38690 | GEO | 2013/06/06

SECONDARY ACCESSION(S): PRJNA168442

REPOSITORIES: GEO

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The ERRalpha metabolic nuclear receptor controls growth of colon cancer cells

Project description:Estrogen-Related Receptor alpha (ERRÎ±) is a nuclear receptor that acts principally as a regulator of metabolism processes particularly in tissues subjected to high-energy demand. Besides its implication in energy metabolism and mitochondrial biogenesis, ERRÎ± was recently associated with tumorigenesis. Notably, increased expression of ERRÎ± was noted in different cancerous tissues as breast, ovary and colon. However, supplemental studies are required to better understand the role of ERRÎ± in colon carcinoma. We used microarrays to detail gene expression during ERRalpha knockdown in HCT116 cells and identified distinct classes of up and down-regulated genes. Triplicate of HCT116 cell line was infected witn shscrambled(shCTL) and shERRalpha lentivirus and used for RNA extraction and hybridization on Affymetrix microarrays.

2013-06-06 | E-GEOD-38690 | biostudies-arrayexpress

Identification of ERRalpha dependent PGC-1alpha tagret genes

Project description:PGC-1 transcription factor was customized to limit its interations to ERRalpha. This mutant (2x9) was used to dissect the transcription activation patterns that are attributable to the PGC1-ERR interaction and PGC-1 actions that are independent of ERR. Inactive mutant with the deleted LLXXL motifs (L2L3) and wt PGC-1 were used as negative and positive controls respectively. BGAL-expressing construct was used to control for non-specific effects of adenoviral infection. Keywords: ERRalpha, PGC-1alpha, nuclear receptor, orphan nuclear receptor, coactivator, transcription factors

2006-11-10 | GSE5968 | GEO

ERRalpha mediates metabolic adaptations that drive lapatinib resistance in breast cancer (ERRalpha binding profiles in breast cancer cells by ChIP-seq)

Project description:Ablation of ERRalpha significantly delays ERBB2-induced mammary tumorigenesis and ERRalpha regulates genes of the ERBB2 amplicon. To further investigate the relationship between ERRalpha activity and RTK signaling, we mapped ERRalpha binding sites in SKBr3 cells upon EGF treatment or heregulin treatment. Inhibition of ERBB2 signaling using the RTK inhibitor lapatinib impacts on ERRalpha stability, while cells resistant to lapatinib treatment exhibit restored ERRalpha expression. We therefore mapped ERRalpha binding sites in parental (sensitive) cells (pSKBr3) as well as in lapatinib-resistant cells (LRSKBr3).

2016-06-15 | GSE81651 | GEO

The function of ERRalpha in viral infection

2015-06-09 | GSE69661 | GEO

Cross-talk between Estrogen Receptor-related Receptor alpha (ERRalpha) and Estrogen Receptor (ERalpha) pathways.

Project description:Orphan nuclear receptor estrogen-related receptor alpha (ERRα) has recently been shown to carry negative prognostic significance in breast and ovarian cancers. The specific role of ERRα in tumor growth and progression, however, is yet to be fully understood. The significant homology between estrogen receptor alpha (ERα) and ERRα initially suggested that these receptors may share similar transcriptional targets. Using the well-characterized ERα-positive MCF-7 breast cancer cell line, we sought to gain a genome-wide picture of ERα-ERRα cross-talk using an unbiased microarray approach. Since a small molecule ligand has not been identified for ERRα, its transcriptional activity in these studies was induced using its known coactivator PGC-1α (peroxisome proliferator-activated receptor-γ coactivator-1α) as a protein ligand. Both wild-type PGC1, as well as ERRa-specific variant (PGC1 2x9) were used to activate ERRa. Non-NR-dependent activities of PGC-1α were controlled for using a variant PGC-1α in which the leucines within the NR-interacting domain had been mutated to alanines (L2L3M). Beta-galactosidase (BGAL) overexpression was used as a non-specific background control. Activation of endogenous ER was achieved by treatment with 10 nM estadiol. Keywords: Response to stimulus

2008-08-25 | GSE11266 | GEO

ERRalpha mediates metabolic adaptations that drive lapatinib resistance in breast cancer (gene expression profiles)

Project description:Ablation of ERRalpha significantly delays ERBB2-induced mammary tumorigenesis and ERRalpha regulates genes of the ERBB2 amplicon. To further investigate the relationship between ERRalpha activity and RTK signaling, we depleted ERRalpha in SKBr3 cells upon serum starvation, EGF treatment or heregulin treatment. Inhibition of ERBB2 signaling using the RTK inhibitor lapatinib impacts on ERRalpha stability. Since we have shown that the development of lapatinib-resistance restaures the expression of ERRalpha in breast cancer cells, we performed depletion of ERRalpha in SKBr3 cells that have developped resistance to lapatinib treatment in order to identify a potential reprogramming of ERRa transcriptional activity associated to lapatinib resistance,

2016-06-15 | GSE81546 | GEO

Transcription profiling of mouse hearts from mutants lacking estrogen-related receptor alpha (ERRalpha), a nuclear receptor

Project description:Total RNA was isolated from 3 WT and 3 ERRalpha null hearts and independent hybridizations were performed using MOE430 2.0 microarrays. Expression profiling was conducted to determine changes in gene expression in hearts lacking ERRa. The expression of genes involved in heart and muscle development, muscle contraction, lipid metabolism, OxPhos, protein metabolism and transcription were affected by the loss of ERRa. Experiment Overall Design: 3 hearts from WT and 3 hearts from ERRalpha-null mice were used in the study. The expression of genes in the ERRalpha KO hearts were compared to the reference WT hearts.

2007-11-10 | E-GEOD-7196 | biostudies-arrayexpress

ERRα fosters running endurance by driving myofiber aerobic transformation and fuel efficiency

Project description:Objective: Estrogen related receptor α (ERRα) occupies a central node in the transcriptional control of energy metabolism, including in skeletal muscle, but whether modulation of its activity can directly contribute to extend endurance to exercise remains to be investigated. The goal of this study was to characterize the benefit of mice engineered to express a physiologically relevant activated form of ERRα on skeletal muscle exercise metabolism and performance. Methods: We recently shown that mutational inactivation of three regulated phosphosites in the amino terminal domain of the nuclear receptor ERRα impedes its degradation, leading to an accumulation of ERRα proteins and perturbation of metabolic homeostasis in ERRα3SA mutant mice. Herein, we used a multi-omics approach in combination with physical endurance tests to ascertain the consequences of expressing the constitutively active phospho-deficient ERRα3SA form on muscle exercise performance and energy metabolism. Results: Genetic heightening of ERRα activity enhanced exercise capacity, fatigue-resistance, and endurance. This phenotype resulted from extensive reprogramming of ERRα global DNA occupancy and transcriptome in muscle leading to an increase in oxidative fibers, mitochondrial biogenesis, fatty acid oxidation, and lactate homeostasis. Conclusion: Our findings support the potential to enhance physical performance and exercise-induced health benefits by targeting molecular pathways regulating ERRα transcriptional activity.

2023-10-11 | GSE219046 | GEO

ERRalpha mediates metabolic adaptations that drive lapatinib resistance in breast cancer (ERRalpha binding profiles in breast cancer cells by ChIP-seq)

2016-06-15 | E-GEOD-81651 | biostudies-arrayexpress

The function of ERRalpha in viral infection

Project description:To explore the function of ERRalpha in viral infection, we compared the cDNA expression profile of ERRalpha knockdown 293T cells and control 293T cells. The cells infected with VSV for 12 h or left uninfected were collected and RNA was extracted by Trizol. Viral infection induced gene expression in ERRalpha knockdown 293T cells or control 293T cells were measured at 0 and 12 hours.

2015-06-09 | E-GEOD-69661 | biostudies-arrayexpress

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