Tumorigenic Role of Orphan Nuclear Receptor NR0B1 in Lung Adenocarcinoma

Oda, Tomoaki; Tian, Tian; Inoue, Masayoshi; Ikeda, Jun‐ichiro; Qiu, Ying; Okumura, Meinoshin; Aozasa, Katsuyuki; Morii, Eiichi

doi:10.2353/ajpath.2009.090010

Cited by 30 publications

(35 citation statements)

References 43 publications

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“…However, in line with previous investigations [27][28][29][30][31][32][33][34][35][36][37], we found the expression of NR0B1, E2F3, and EZH2 to be much less sensitive and specific for the diagnosis of ES than that of NKX2.2.…”

Section: Discussionsupporting

confidence: 90%

The combination of CD99 and NKX2.2, a transcriptional target of EWSR1-FLI1, is highly specific for the diagnosis of Ewing sarcoma

et al. 2014

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Ewing sarcoma (ES) is a high-grade malignant neoplasm primarily affecting children and young adults. The diagnosis of ES is often difficult because of its broad differential diagnosis comprising a diverse group of small round cell tumors (SRCTs). Although the identification of tumor type-specific fusion genes by molecular testing is the gold standard for the diagnosis of ES, such approaches are not always available in a routine pathology practice. Thus, a reliable immunohistochemical marker is required. A recent study using a limited number of tumor samples has shown that NKX2.2, a putative transcriptional target of EWSR1-FLI1, is a useful marker for the diagnosis of ES. In the present study, the immunohistochemical expression of NKX2.2 was evaluated on 46 genetically confirmed ES and 85 non-ES SRCTs, together with comparative assessment of CD99 and other molecular targets of EWSR1-FLI1, including NR0B1, E2F3, and EZH2. NKX2.2 was expressed in 37 (80 %) of the ES samples with a mostly diffuse and strong staining pattern, and 14 (16 %) of the non-ES SRCTs, including olfactory neuroblastomas, extraskeletal myxoid chondrosarcoma, mesenchymal chondrosarcoma, small cell carcinomas, and Merkel cell carcinoma, also expressed this marker. The sensitivity and specificity of the NKX2.2 expression in this cohort were 80 and 84 %, respectively. The specificity when combined with CD99 was 98 %, with exceptional expression of both markers in only two non-ES SRCTs, including one case each of mesenchymal chondrosarcoma and small cell carcinoma. NR0B1, E2F3, and EZH2 were less sensitive for specific markers for ES when applied singly or in any combination. In conclusion, the study reinforces that NKX2.2 is a useful immunohistochemical marker for ES, and that the combination of CD99 and NKX2.2 is a powerful diagnostic tool that can differentiate ES from other SRCTs.

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Section: Discussionsupporting

confidence: 90%

The combination of CD99 and NKX2.2, a transcriptional target of EWSR1-FLI1, is highly specific for the diagnosis of Ewing sarcoma

et al. 2014

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“…expression appears to be induced via epigenetic reprogramming i.e. demethylation of the DAX-1 promoter leads to increased levels of DAX-1, an unfavorable prognostic marker in lung cancer [91] (Fig. 4B).…”

Section: Nr0b In Cancer-oncogenic Versus Tumor Suppressor Actionmentioning

confidence: 98%

Ligand-independent actions of the orphan receptors/corepressors DAX-1 and SHP in metabolism, reproduction and disease

Ehrlund

Treuter

2012

The Journal of Steroid Biochemistry and Molecular Biology

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“…A higher expression level of DAX1 was found to be correlated with higher rates of lymph node metastasis in lung adenocarcinoma. Knockdown of DAX1 can significantly inhibit the invasion capability of lung cancer cells [127]. DAX1 is induced by the oncoprotein chimerical transcription factors (EWS/FLI1) and highly expressed in Ewing's tumors and play an important role in cell-cycle progression [128,129].…”

Section: Dax1mentioning

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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Tumorigenic Role of Orphan Nuclear Receptor NR0B1 in Lung Adenocarcinoma

Cited by 30 publications

References 43 publications

The combination of CD99 and NKX2.2, a transcriptional target of EWSR1-FLI1, is highly specific for the diagnosis of Ewing sarcoma

The combination of CD99 and NKX2.2, a transcriptional target of EWSR1-FLI1, is highly specific for the diagnosis of Ewing sarcoma

Ligand-independent actions of the orphan receptors/corepressors DAX-1 and SHP in metabolism, reproduction and disease

The emerging roles of orphan nuclear receptors in prostate cancer

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