Erythroid differentiation regulator 1, an interleukin 18-regulated gene, acts as a metastasis suppressor in melanoma

J Invest Dermatol. 2011 Oct;131(10):2096-104. doi: 10.1038/jid.2011.170. Epub 2011 Jun 23.


Erythroid differentiation regulator (Erdr1) was first discovered in mouse leukemia cell lines and functions as a stress-related survival factor. This study investigated whether Erdr1 regulates murine melanoma progression, as well as the mechanism involved in Erdr1-regulated metastasis. The expression of Erdr1 is negatively correlated with IL-18 expression, which has a pro-cancer effect in melanoma. To study the role of Erdr1 as an anti-cancer factor, cell migration, invasion, and proliferation were measured. Erdr1 overexpression markedly inhibited the level of cell migration, invasion, and proliferation in B16F10 cells in vitro. In addition, Erdr1 overexpression significantly suppressed melanoma lung colonization, metastasis, and tumor growth in vivo. To identify the factors involved in Erdr1-reduced metastasis, heat shock protein 90 (HSP90), a well-known stress protein and contributor to tumor metastasis, was examined. We found that HSP90 was significantly decreased in Erdr1-overexpressing cells. Functional analysis demonstrated that HSP90 small-interfering RNA transfection reduced the migration ability and metastasis of melanoma. In conclusion, Erdr1 shows a powerful anti-metastasis effect that leads to the ability to reduce the metastatic potential of murine malignant melanoma cells. Erdr1 is an anti-metastatic factor that may be a possible therapeutic target for treatment of melanoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement
  • Cell Proliferation
  • HSP90 Heat-Shock Proteins / metabolism
  • Humans
  • Interleukin-18 / metabolism*
  • Lung Neoplasms / secondary
  • Melanoma / genetics*
  • Melanoma / therapy
  • Melanoma, Experimental
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Mice
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • RNA, Small Interfering / metabolism
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / therapy
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / physiology*


  • HSP90 Heat-Shock Proteins
  • Interleukin-18
  • Membrane Proteins
  • RNA, Small Interfering
  • Tumor Suppressor Proteins
  • erythroid differentiation regulator 1, mouse