Dual Roles of Orphan Nuclear Receptor TR3/Nur77/NGFI-B in Mediating Cell Survival and Apoptosis

Niu, Gengming; Lü, Lei; Gan, Jing; Zhang, Di; Liu, Jingzheng; Huang, Guangjian

doi:10.1016/b978-0-12-800177-6.00007-4

Cited by 31 publications

(16 citation statements)

References 131 publications

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“…Subsequently, the overexpression of Nur77 in breast cancer cell xenografts was reported to alter the inflammatory response and increase the risk of metastatic disease in mice ( 30 ). Another study suggested that the cytoplasmic expression of Nur77 can induce apoptosis in breast cancer cells ( 31 ). Notably, one report demonstrated that Nur77 is involved in the migration of transforming growth factor-β-induced breast cancer cells ( 32 ); furthermore, this process is dependent on p38α ( 33 ).…”

Section: Structure Expression and Localization Of Nur77mentioning

confidence: 99%

Characteristics of Nur77 and its ligands as potential anticancer compounds (Review)

Chen

2018

Mol Med Report

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Nuclear receptor subfamily 4 group A member 1 (NR4A1; also termed Nur77/TR3/NGFIB), a member of the nuclear receptor superfamily, is expressed as an early response gene to regulate the expression of multiple target genes. Nur77 has the typical structure of a nuclear receptor, including an N-terminal domain, a DNA binding domain, and a ligand-binding domain. The expression and localization of Nur77 are closely associated with its roles in cell proliferation and apoptosis. Nur77 was first identified as an orphan receptor, the endogenous ligand of which has not yet been identified; however, an increasing number of compounds targeting Nur77 have been reported to have beneficial effects in the treatment of cancer and other diseases. This review provides a brief overview of the identification, structure, expression and localization, transcriptional role and non-genomic function of Nur77, and summarizes the ligands that have been shown to interact with Nur77, including cytosporone B, cisplatin, TMPA, PDNPA, CCE9, THPN, Z-ligustilide, celastrol and bisindole methane compounds, which may potentially be used to treat cancer in humans.

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Section: Structure Expression and Localization Of Nur77mentioning

confidence: 99%

Characteristics of Nur77 and its ligands as potential anticancer compounds (Review)

Chen

2018

Mol Med Report

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“…Nur77 plays a critical role in inflammation and in cellular processes, such as proliferation, differentiation, survival and death (9). Previous researchers investigating Nur77 have focused mostly on neurological disorders, cardiovascular diseases and cancer (10). Nur77 expression has been described in lung tissue and lung epithelial cells.…”

Section: Introductionmentioning

confidence: 99%

Nur77 promotes cigarette smoke‑induced autophagic cell death by increasing the dissociation of Bcl2 from Beclin-1

et al. 2019

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Chronic obstructive pulmonary disease (COPD) is characterized by partially reversible airflow limitation and persistent alveolar destruction, and autophagy is involved in the pathogenesis of cigarette smoke (CS)-induced COPD. Nuclear receptor 77 (Nur77) participates in a number of biological processes, including apoptosis, autophagy and in disease pathogenesis; however, the role of Nur77 in COPD remains unknown. Thus, in this study, we aimed to elucidate the role of Nur77 in COPD. We report that CS promotes Nur77 expression and nuclear export in vivo and in vitro , which increases cigarette smoke extract (CSE)-induced autophagy. In addition, we found that lung tissues, human bronchial epithelial (HBE) cells and A549 cells exposed to CS or CSE expressed lower levels of LC3 and Beclin-1 and contained fewer autophagosomes following Nur77 knockdown with siRNA-Nur77. Moreover, a co-immunoprecipitation assay demonstrated that CSE promoted autophagy, partly by accelerating the interaction between Nur77 and Bcl2, in turn leading to the increased dissociation of Bcl2 from Beclin-1; by contrast, leptomycin B (LMB) suppressed the dissociation of Bcl2 from Beclin-1. Taken together, the findings of this study demonstrate that Nur77 is involved in the CSE-induced autophagic death of lung cells, and that this process is partially dependent on the increased interaction between Nur77 and Bcl2, and on the dissociation of Bcl2 from Beclin-1. This study illustrates the role of Nur77 in bronchial and alveolar destruction following exposure to CS.

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“…NR4A1 overexpression in breast cancer cell line xenografts results in altered inflammatory response and increased risk for metastatic disease [29]. However, cytoplasmic NR4A1 can contribute to apoptosis of breast cancer cells [22]. We were able to show that NR4A1 expression at baseline is relatively high within normal ovarian tissue as compared to a number of other human tissue types.…”

Section: Discussionmentioning

confidence: 95%

High expression of orphan nuclear receptor NR4A1 in a subset of ovarian tumors with worse outcome

Delgado

Boisen

Laskey

et al. 2016

Gynecologic Oncology

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Objective Nuclear receptors (NRs) play a vital role in the development and progression of several cancers including breast and prostate. Using TCGA data, we sought to identify critical nuclear receptors in high grade serous ovarian cancers (HGSOC) and to confirm these findings using in vitro approaches. Methods In silico analysis of TCGA data was performed to identify relevant NRs in HGSOC. Ovarian cancer cell lines were screened for NR expression and functional studies were performed to determine the significance of these NRs in ovarian cancers. NR expression was analyzed in ovarian cancer tissue samples using immunohistochemistry to identify correlations with histology and stage of disease. Results The NR4A family of NRs was identified as a potential driver of ovarian cancer pathogenesis. Overexpression of NR4A1 in particular correlated with worse progression free survival. Endogenous expression of NR4A1 in normal ovarian samples was relatively high compared to that of other tissue types, suggesting a unique role for this orphan receptor in the ovary. Expression of NR4A1 in HGSOC cell lines as well as in patient samples was variable. NR4A1 primarily localized to the nucleus in normal ovarian tissue while co-localization within the cytoplasm and nucleus was noted in ovarian cancer cell lines and patient tissues. Conclusions NR4A1 is highly expressed in a subset of HGSOC samples from patients that have a worse progression free survival. Studies to target NR4A1 for therapeutic intervention should include HGSOC.

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Dual Roles of Orphan Nuclear Receptor TR3/Nur77/NGFI-B in Mediating Cell Survival and Apoptosis

Cited by 31 publications

References 131 publications

Characteristics of Nur77 and its ligands as potential anticancer compounds (Review)

Characteristics of Nur77 and its ligands as potential anticancer compounds (Review)

Nur77 promotes cigarette smoke‑induced autophagic cell death by increasing the dissociation of Bcl2 from Beclin-1

High expression of orphan nuclear receptor NR4A1 in a subset of ovarian tumors with worse outcome

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