Orphan nuclear receptor Nurr1 as a potential novel marker for progression in human pancreatic ductal adenocarcinoma

Li, Ji; Chen, Gong; Ge, Lu; Song, Lin-Ping; Chen, Fen-Fen; Jin, Chunjing; Zhou, Guoqing

doi:10.3892/etm.2016.3968

Cited by 11 publications

(11 citation statements)

References 29 publications

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“…NR4ATKO CAR-T cells exhibited better performance on inducing tumor regression and prolonged the survival of tumor-bearing mice compared to those with WT CAR-TILs and single-gene knockouts. Briefly, these results suggest that the efficacy of existing immunotherapies on solid tumors can be improved by additional targeting of NFAT and NR4A ( Figure 2 ), whose expressions are also correlated with tumor initiation and progression in PDAC [ 165 ]…”

Section: Transcriptional and Epigenetic Reprogramming Of T-cell Exmentioning

confidence: 99%

Mechanisms of T-Cell Exhaustion in Pancreatic Cancer

Saka

Gökalp

Piyade

et al. 2020

Cancers

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T-cell exhaustion is a phenomenon that represents the dysfunctional state of T cells in chronic infections and cancer and is closely associated with poor prognosis in many cancers. The endogenous T-cell immunity and genetically edited cell therapies (CAR-T) failed to prevent tumor immune evasion. The effector T-cell activity is perturbed by an imbalance between inhibitory and stimulatory signals causing a reprogramming in metabolism and the high levels of multiple inhibitory receptors like programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), and Lymphocyte-activation gene 3 (Lag-3). Despite the efforts to neutralize inhibitory receptors by a single agent or combinatorial immune checkpoint inhibitors to boost effector function, PDAC remains unresponsive to these therapies, suggesting that multiple molecular mechanisms play a role in stimulating the exhaustion state of tumor-infiltrating T cells. Recent studies utilizing transcriptomics, mass cytometry, and epigenomics revealed a critical role of Thymocyte selection-associated high mobility group box protein (TOX) genes and TOX-associated pathways, driving T-cell exhaustion in chronic infection and cancer. Here, we will review recently defined molecular, genetic, and cellular factors that drive T-cell exhaustion in PDAC. We will also discuss the effects of available immune checkpoint inhibitors and the latest clinical trials targeting various molecular factors mediating T-cell exhaustion in PDAC.

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Section: Transcriptional and Epigenetic Reprogramming Of T-cell Exmentioning

confidence: 99%

Mechanisms of T-Cell Exhaustion in Pancreatic Cancer

Saka

Gökalp

Piyade

et al. 2020

Cancers

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“…Studies have further examined the roles of Nr4a1 and Nr4a3 in AML cell lines and other immune cell cancers. Nr4a1 downregulates proliferation associated genes such as c-MYC, BCL2, CBFA2T3 and CSF1R and the myeloid transcription factor PU.1 in Kasumi-1 cells [47]. Nr4a1 and Nr4a3 overexpression decreased Kasumi-1 proliferation and cell viability.…”

Section: Proliferationmentioning

confidence: 99%

Function of Nr4a Orphan Nuclear Receptors in Proliferation, Apoptosis and Fuel Utilization Across Tissues

Herring

Elison

Tessem

2019

Cells

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The Nr4a family of nuclear hormone receptors is composed of three members—Nr4a1/Nur77, Nr4a2/Nurr1 and Nr4a3/Nor1. While currently defined as ligandless, these transcription factors have been shown to regulate varied processes across a host of tissues. Of particular interest, the Nr4a family impinge, in a tissue dependent fashion, on cellular proliferation, apoptosis and fuel utilization. The regulation of these processes occurs through both nuclear and non-genomic pathways. The purpose of this review is to provide a balanced perspective of the tissue specific and Nr4a family member specific, effects on cellular proliferation, apoptosis and fuel utilization.

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“…Overexpression of Nurr1 has been shown to promote cancer cell proliferation, invasion and anchorage-independent growth [ 10 , 11 ]. It also enhances cell survival by suppressing apoptosis [ 12 , 13 ]. Apart from augmenting cancer aggressiveness, Nurr1 confers therapeutic resistance to cancer cells, including radioresistance and chemoresistance to 5-fluorouracil [ 14 , 15 , 16 ].…”

Section: Expression and Function Of Nurr1 In Cancermentioning

confidence: 99%

“…Several pro-inflammatory molecules including prostaglandin E 2 and thromboxane A2 were reported to induce Nurr1 expression, which can lead to carcinogenesis [ 17 , 18 ]. Furthermore, the expression of Nurr1 is correlated with different clinicopathological parameters in multiple cancers [ 12 , 13 , 14 ]. Since Nurr1 is generally considered to be a transcription factor, its roles in the cytosol are not well characterized.…”

Section: Expression and Function Of Nurr1 In Cancermentioning

confidence: 99%

“…Nurr1 is a significant independent prognostic indicator in patients with pancreatic ductal adenocarcinoma. High Nurr1 expression in this cancer has been correlated with histological subtypes with higher grade, higher stage, high Ki-67 expression, and poor overall survival [ 13 ]. In addition, functional studies revealed that silencing of Nurr1 promotes apoptosis and attenuates cell migration, invasion, and proliferation.…”

Section: Expression and Function Of Nurr1 In Cancermentioning

confidence: 99%

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Role of Nurr1 in Carcinogenesis and Tumor Immunology: A State of the Art Review

Wan

Siu

Leung

et al. 2020

Cancers

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Nuclear receptor related-1 protein (Nurr1), coded by an early response gene, is involved in multiple cellular and physiological functions, including proliferation, survival, and self-renewal. Dysregulation of Nurr1 has been frequently observed in many cancers and is attributed to multiple transcriptional and post-transcriptional mechanisms. Besides, Nurr1 exhibits extensive crosstalk with many oncogenic and tumor suppressor molecules, which contribute to its potential pro-malignant behaviors. Furthermore, Nurr1 is a key player in attenuating antitumor immune responses. It not only potentiates immunosuppressive functions of regulatory T cells but also dampens the activity of cytotoxic T cells. The selective accessibility of chromatin by Nurr1 in T cells is closely associated with cell exhaustion and poor efficacy of cancer immunotherapy. In this review, we summarize the reported findings of Nurr1 in different malignancies, the mechanisms that regulate Nurr1 expression, and the downstream signaling pathways that Nurr1 employs to promote a wide range of malignant phenotypes. We also give an overview of the association between Nurr1 and antitumor immunity and discuss the inhibition of Nurr1 as a potential immunotherapeutic strategy.

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Orphan nuclear receptor Nurr1 as a potential novel marker for progression in human pancreatic ductal adenocarcinoma

Cited by 11 publications

References 29 publications

Mechanisms of T-Cell Exhaustion in Pancreatic Cancer

Mechanisms of T-Cell Exhaustion in Pancreatic Cancer

Function of Nr4a Orphan Nuclear Receptors in Proliferation, Apoptosis and Fuel Utilization Across Tissues

Role of Nurr1 in Carcinogenesis and Tumor Immunology: A State of the Art Review

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