c-Rel and its many roles in cancer: an old story with new twists

Br J Cancer. 2016 Jan 12;114(1):1-6. doi: 10.1038/bjc.2015.410.


When the genes encoding NF-κB subunits were first isolated, their homology to the previously identified c-Rel proto-oncogene and its viral homologue v-Rel was clear. This provided the first indication that these transcription factors also had a role in cancer. Because of its homology to v-Rel, which transforms chicken B cells together with the important role c-Rel can have as a regulator of B- and T-cell proliferation, most attention has focussed on its role in B-cell lymphomas, where the REL gene is frequently amplified. However, a growing number of reports now indicate that c-Rel has important functions in many solid tumours, although studies in mice suggest it may not always function as an oncogene. Moreover, c-Rel is a critical regulator of fibrosis, which provides an environment for tumour development in many settings. Overall, c-Rel is emerging as a complex regulator of tumorigenesis, and there is still much to learn about its functions in human malignancies and the response to cancer therapies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Fibrosis
  • Genes, p53 / physiology
  • Genes, rel / physiology
  • Humans
  • Lymphoma, B-Cell / etiology
  • Mice
  • Neoplasms / etiology*
  • Neoplasms / therapy
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-rel / chemistry
  • Proto-Oncogene Proteins c-rel / physiology*


  • MAS1 protein, human
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-rel