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

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.

• Authors: Jordan A Beard, Alexa Tenga, Taosheng Chen
• Journal: Cellular signalling (Cell Signal) Vol. 27 Issue 2 Pg. 257-66 (Feb 2015) ISSN: 1873-3913 [Electronic] England
• PMID: 25446259 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Hypoxia-Inducible Factor 1
• Nuclear Receptor Subfamily 4, Group A, Member 1
• Tumor Suppressor Protein p53
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases
• Mitogen-Activated Protein Kinases

Topics

• Apoptosis
• Humans
• Hypoxia-Inducible Factor 1 (metabolism)
• Mitogen-Activated Protein Kinases (metabolism)
• Neoplasms (metabolism, pathology)
• Nuclear Receptor Subfamily 4, Group A, Member 1 (metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction
• TOR Serine-Threonine Kinases (metabolism)
• Tumor Suppressor Protein p53 (metabolism)