There and back again: The journey of the estrogen-related receptors in the cancer realm

Tam, Ingrid S; Giguère, Vincent

doi:10.1016/j.jsbmb.2015.06.009

Cited by 43 publications

(48 citation statements)

References 111 publications

(161 reference statements)

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“…ERRs regulate cancer cell growth and tumor progression by manipulating expression of genes involved in aerobic glycolysis that provide energy for rapid growth and proliferation of cancer cells, genes responsible for glucose and glutamine uptake for using of alternative source of energy, and also gene networks in lipid synthesis which is required for cell mass building during the rapid division/proliferation of cancer cells [55]. Multiple functional analyses indicate that ERRs favor to cooperate with certain oncogenes or oncogenic signals to modulate some key metabolic regulators (e.g.…”

Section: Errsmentioning

confidence: 99%

The emerging roles of orphan nuclear receptors in prostate cancer

Cheung

Wang

et al. 2016

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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Orphan nuclear receptors are members of the nuclear receptor (NR) superfamily and are so named because their endogenous physiological ligands are either unknown or may not exist. Because of their important regulatory roles in many key physiological processes, dysregulation of signalings controlled by these receptors is associated with many diseases including cancer. Over years, studies of orphan NRs have become an area of great interest because their specific physiological and pathological roles have not been well-defined, and some of them are promising drug targets for diseases. The recently identified synthetic small molecule ligands, acting as agonists or antagonists, to these orphan NRs not only help to understand better their functional roles but also highlight that the signalings mediated by these ligand-independent NRs in diseases could be therapeutically intervened. This review is a summary of the recent advances in elucidating the emerging functional roles of orphan NRs in cancers, especially prostate cancer. In particular, some orphan NRs, RORγ, TR2, TR4, COUP-IFII, ERRα, DAX1 and SHP, exhibit crosstalk or interference with androgen receptor (AR) signaling in either normal or malignant prostatic cells, highlighting their involvement in prostate cancer progression as androgen and AR signaling pathway play critical roles in this process. We also propose that a better understanding of the mechanism of actions of these orphan NRs in prostate gland or prostate cancer could help to evaluate their potential value as therapeutic targets for prostate cancer.

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Section: Errsmentioning

confidence: 99%

The emerging roles of orphan nuclear receptors in prostate cancer

Cheung

Wang

et al. 2016

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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“…Similarly, increasing the expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PPARGC1A), the protein ligand of ESRRA, increases energy expenditure and reduces obesity [23]. So far, most previous studies of ESRR actions have focused on its role in cancer progression and this topic has been reviewed elsewhere [24][25][26][27][28][29][30][31][32][33][34][35]. There have also been a few studies on its roles in bone and muscle differentiation [36][37][38], trauma/shock [39], and infection [40].…”

Section: Introductionmentioning

confidence: 99%

Estrogen-Related Receptor Alpha: An Under-Appreciated Potential Target for the Treatment of Metabolic Diseases

Tripathi

Yen

Singh

2020

IJMS

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The estrogen-related receptor alpha (ESRRA) is an orphan nuclear receptor (NR) that significantly influences cellular metabolism.ESRRA is predominantly expressed in metabolically-active tissues and regulates the transcription of metabolic genes, including those involved in mitochondrial turnover and autophagy. Although ESRRA activity is well-characterized in several types of cancer, recent reports suggest that it also has an important role in metabolic diseases. This minireview focuses on the regulation of cellular metabolism and function by ESRRA and its potential as a target for the treatment of metabolic disorders.

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“…ERRα is known to regulate the adaptive bioenergetics response [10]. It is widely expressed in both healthy tissues and a range of cancerous cells [11][12][13][14]. Notably, ERRαpositive tumors were associated with more invasive disease and higher risk of recurrences [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

“…It is widely expressed in both healthy tissues and a range of cancerous cells [11][12][13][14]. Notably, ERRαpositive tumors were associated with more invasive disease and higher risk of recurrences [11][12][13]. In addition to angiogenesis, ERRα is mainly linked to tumor cell invasion [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

ERRα promotes breast cancer cell dissemination to bone by increasing RANK expression in primary breast tumors

et al. 2018

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Bone is the most common metastatic site for breast cancer. Estrogen-related-receptor alpha (ERRα) has been implicated in cancer cell invasiveness. Here, we established that ERRα promotes spontaneous metastatic dissemination of breast cancer cells from primary mammary tumors to the skeleton. We carried out cohort studies, pharmacological inhibition, gain-offunction analyses in vivo and cellular and molecular studies in vitro to identify new biomarkers in breast cancer metastases. Meta-analysis of human primary breast tumors revealed that high ERRα expression levels were associated with bone but not lung metastases. ERRα expression was also detected in circulating tumor cells from metastatic breast cancer patients. ERRα overexpression in murine 4T1 breast cancer cells promoted spontaneous bone micro-metastases formation when tumor cells were inoculated orthotopically, whereas lung metastases occurred irrespective of ERRα expression level. In vivo, Rank was identified as a target for ERRα. That was confirmed in vitro in Rankl stimulated tumor cell invasion, in mTOR/pS6K phosphorylation, by transactivation assay, ChIP and bioinformatics analyses. Moreover, pharmacological inhibition of ERRα reduced primary tumor growth, bone micro-metastases formation and Rank expression in vitro and in vivo. Transcriptomic studies and meta-analysis confirmed a positive association between metastases and ERRα/RANK in breast cancer patients and also revealed a positive correlation between ERRα and BRCA1 mut carriers. Taken together, our results reveal a novel ERRα/RANK axis by which ERRα in primary breast cancer promotes early dissemination of cancer cells to bone. These findings suggest that ERRα may be a useful therapeutic target to prevent bone metastases.

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There and back again: The journey of the estrogen-related receptors in the cancer realm

Cited by 43 publications

References 111 publications

The emerging roles of orphan nuclear receptors in prostate cancer

The emerging roles of orphan nuclear receptors in prostate cancer

Estrogen-Related Receptor Alpha: An Under-Appreciated Potential Target for the Treatment of Metabolic Diseases

ERRα promotes breast cancer cell dissemination to bone by increasing RANK expression in primary breast tumors

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