High NR2F2 transcript level is associated with increased survival and its expression inhibits TGF-β-dependent epithelial-mesenchymal transition in breast cancer

Zhang, Cheng; Han, Yong; Huang, Hao; Qu, Like; Shou, Chengchao

doi:10.1007/s10549-014-3095-3

Cited by 27 publications

(25 citation statements)

References 61 publications

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“…Interestingly, the GREB1 gene has recently been reported as an ERα interacting transcriptional co-activator (Mohammed et al, 2013). The NR2F2 gene encodes the COUP-TFII nuclear receptor that has been shown to have a role in breast cancer progression as well (Zhang et al, 2014). …”

Section: Discussionmentioning

confidence: 99%

Enhancer-Mediated Oncogenic Function of the Menin Tumor Suppressor in Breast Cancer

et al. 2017

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SUMMARY While the multiple endocrine neoplasia type 1 (MEN1) gene functions as a tumor suppressor in a variety of cancer types, we explored its oncogenic role in breast tumorigenesis. The MEN1 gene product menin is involved in H3K4 trimethylation and co-activates transcription. We integrated ChIP-seq and RNA-seq data to identify menin target genes. Our analysis revealed that menin-dependent target gene promoters display looping to distal enhancers that are bound by menin, FOXA1 and GATA3. In this fashion, MEN1 co-regulates a proliferative breast cancer-specific gene expression program in ER+ cells. In primary mammary cells MEN1 exerts an anti-proliferative function by regulating a distinct expression signature. Our findings clarify the cell type-specific functions of MEN1 and inform the development of menin-directed treatments for breast cancer.

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Section: Discussionmentioning

confidence: 99%

Enhancer-Mediated Oncogenic Function of the Menin Tumor Suppressor in Breast Cancer

et al. 2017

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“…Furthermore, DEGs were overrepresented as targets of HNF4A, HNF4G, FOXA1, FOXA2 and NR2F2 transcription factors (TFs) (Fig.S5F). These TFs play central roles in cell polarity maintenance and epithelial differentiation [24][25][26], hence downregulation of KDM8 may drive epithelial-mesenchymal transition (EMT) and tumor progression. HNF4A is one of the key TFs responsible for regulating a myriad of hepatic functions including cell junction assembly [26,27].…”

Section: Tumor Suppressive Roles Of Kdm8 Through Cell Cycle Regulatiomentioning

confidence: 99%

Dual prognostic role for 2-oxoglutarate oxygenases in ten diverse cancer types: Implications for cell cycle regulation and cell adhesion maintenance

Forde

Lai

2018

Preprint

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Objectives: Tumor hypoxia is associated with metastasis and resistance to chemotherapy and radiotherapy. Genes involved in oxygen-sensing are clinically relevant and have significant implications on prognosis. Methods:We identified of two signatures, signature 1 (good prognosis) and signature 2 (adverse prognosis), each consisting of 5 genes using three pancreatic cancer cohorts (n=681). We validated the signatures' performance in predicting survival in ten cancers using Cox regression and receiver operating characteristic (ROC) analyses. Results: Signature 1 and signature 2 were associated with good and poor overall survival respectively. Prognosis of signature 1 in 8 cohorts representing 6 cancers (n=2,627): bladder (hazard ratio [HR]=0.68, P=0.039), papillary renal cell (HR=0.35, P=0.013), liver (HR=0.64, P=0.033 and HR=0.49, P=0.025), lung (HR=0.66, P=0.014) and pancreatic (HR=0.42, P<0.001 and HR=0.64, P=0.04) and endometrial (HR=0.40, P<0.001). Prognosis of signature 2 in 12 cohorts representing 9 cancers (n=4,134): bladder (HR=1.46, P=0.039), cervical (HR=1.97, P=0.035), head and neck (HR=1.39, P=0.038), renal clear cell (HR=1.47, P=0.012), papillary renal cell (HR=3.89, P=0.0015), liver (HR=5.10, P<0.0001 and HR=2.26, P<0.001), lung (HR=1.54, P=0.011), pancreatic (HR=2.09, P=0.002, HR=1.46, P=0.018, and HR=1.99, P<0.0001) and stomach (HR=1.78, P=0.004). Multivariate Cox regression confirmed independent clinical relevance of signatures in these cancers. ROC analyses confirmed superior performance of signatures to current tumor staging benchmarks. KDM8 is a potential tumor suppressor downregulated in liver and pancreatic cancers and is an independent prognostic factor. KDM8 expression negatively correlated with cell cycle regulators. Low KDM8 in tumors was associated with loss of cell adhesion phenotype through HNF4A signaling. Conclusions: Pan-cancer signatures of oxygen-sensing genes used for risk assessment in 10 cancers (n=6,761) could guide individualized treatment plans. Low Risk, PCDHA1 WT Low Risk, PCDHA1 mutant High Risk, PCDHA1 WT High Risk, PCDHA1 mutant Low Risk, PCDHA1 WT Low Risk, PCDHA1 mutant High Risk, PCDHA1 WT High Risk, PCDHA1 mutant

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“…NR2F2 silencing does not affect the growth/survival, while it increases MCF-7 and ER − / MDA-MB-231 cell-migration. NR2F2 inhibits TGFβ-dependent EMT in both cell-lines [126]. NR2F2 down-regulation is associated with anti-estrogen resistance and NR2F2 over-expression reinstates sensitivity [127].…”

Section: Orphan Receptorsmentioning

confidence: 99%

Lipid-sensors, enigmatic-orphan and orphan nuclear receptors as therapeutic targets in breast-cancer

et al. 2016

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Breast-cancer is heterogeneous and consists of various groups with different biological characteristics. Innovative pharmacological approaches accounting for this heterogeneity are needed. The forty eight human Nuclear-Hormone-Receptors are ligand-dependent transcription-factors and are classified into Endocrine-Receptors, Adopted-Orphan-Receptors (Lipid-sensors and Enigmatic-Orphans) and Orphan-receptors. Nuclear-Receptors represent ideal targets for the design/synthesis of pharmacological ligands. We provide an overview of the literature available on the expression and potential role played by Lipid-sensors, Enigmatic-Orphans and Orphan-Receptors in breast-cancer. The data are complemented by an analysis of the expression levels of each selected Nuclear-Receptor in the PAM50 breast-cancer groups, following re-elaboration of the data publicly available. The major aim is to support the idea that some of the Nuclear-Receptors represent largely unexploited therapeutic-targets in breast-cancer treatment/chemo-prevention. On the basis of our analysis, we conclude that the Lipid-Sensors, NR1C3, NR1H2 and NR1H3 are likely to be onco-suppressors in breast-cancer. The Enigmatic-Orphans, NR1F1 NR2A1 and NR3B3 as well as the Orphan-Receptors, NR0B1, NR0B2, NR1D1, NR2F1, NR2F2 and NR4A3 exert a similar action. These Nuclear-Receptors represent candidates for the development of therapeutic strategies aimed at increasing their expression or activating them in tumor cells. The group of Nuclear-Receptors endowed with potential oncogenic properties consists of the Lipid-Sensors, NR1C2 and NR1I2, the Enigmatic-Orphans, NR1F3, NR3B1 and NR5A2, as well as the Orphan-Receptors, NR2E1, NR2E3 and NR6A1. These oncogenic Nuclear-Receptors should be targeted with selective antagonists, reverse-agonists or agents/strategies capable of reducing their expression in breast-cancer cells.

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High NR2F2 transcript level is associated with increased survival and its expression inhibits TGF-β-dependent epithelial-mesenchymal transition in breast cancer

Cited by 27 publications

References 61 publications

Enhancer-Mediated Oncogenic Function of the Menin Tumor Suppressor in Breast Cancer

Enhancer-Mediated Oncogenic Function of the Menin Tumor Suppressor in Breast Cancer

Dual prognostic role for 2-oxoglutarate oxygenases in ten diverse cancer types: Implications for cell cycle regulation and cell adhesion maintenance

Lipid-sensors, enigmatic-orphan and orphan nuclear receptors as therapeutic targets in breast-cancer

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