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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Apoptosis
  • Humans
  • Hypoxia-Inducible Factor 1 / metabolism
  • Mitogen-Activated Protein Kinases / metabolism
  • Neoplasms / metabolism
  • Neoplasms / 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

Substances

  • Hypoxia-Inducible Factor 1
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • Tumor Suppressor Protein p53
  • Phosphatidylinositol 3-Kinases
  • TOR Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases