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Cell Signal. 2015 Feb;27(2):257-66. doi: 10.1016/j.cellsig.2014.11.009. Epub 2014 Nov 15.

The interplay of NR4A receptors and the oncogene-tumor suppressor networks in cancer.

Author information

1
Department of Chemical Biology & Therapeutics, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS 1000, Memphis, TN 38105, USA; Integrated Biomedical Sciences Program, University of Tennessee Health Science Center, 920 Madison Avenue, Suite 407, Memphis, TN 38163, USA.
2
Department of Chemical Biology & Therapeutics, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS 1000, Memphis, TN 38105, USA; Integrated Biomedical Sciences Program, University of Tennessee Health Science Center, 920 Madison Avenue, Suite 407, Memphis, TN 38163, USA. Electronic address: taosheng.chen@stjude.org.

Abstract

Nuclear receptor (NR) subfamily 4 group A (NR4A) is a family of three highly homologous orphan nuclear receptors that have multiple physiological and pathological roles, including some in cancer. These NRs are reportedly dysregulated in multiple cancer types, with many studies demonstrating pro-oncogenic roles for NR4A1 (Nur77) and NR4A2 (Nurr1). Additionally, NR4A1 and NR4A3 (Nor-1) are described as tumor suppressors in leukemia. The dysregulation and functions of the NR4A members are due to many factors, including transcriptional regulation, protein-protein interactions, and post-translational modifications. These various levels of intracellular regulation result from the signaling cross-talk of the NR4A members with various signaling pathways, many of which are relevant to cancer and likely explain the family members' functions in oncogenesis and tumor suppression. In this review, we discuss the multiple functions of the NR4A receptors in cancer and summarize a growing body of scientific literature that describes the interconnectedness of the NR4A receptors with various oncogene and tumor suppressor pathways.

KEYWORDS:

NR4A; Nuclear receptor; Nur77; Nurr1; Oncogene; Tumour suppressor

PMID:
25446259
PMCID:
PMC4276441
DOI:
10.1016/j.cellsig.2014.11.009
[Indexed for MEDLINE]
Free PMC Article

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