EphA2 is a critical oncogene in melanoma

Oncogene. 2011 Dec 15;30(50):4921-9. doi: 10.1038/onc.2011.210. Epub 2011 Jun 13.

Abstract

EphA2 is a member of the Eph family of receptor tyrosine kinases and is highly expressed in many aggressive cancer types, including melanoma. We recently showed that EphA2 is also upregulated by ultraviolet radiation and is able to induce apoptosis. These findings suggest that EphA2 may have different, even paradoxical, effects on viability depending on the cellular context and that EphA2 mediates a delicate balance between life and death of the cell. To functionally clarify EphA2's role in melanoma, we analyzed a panel of melanoma cell lines and found that EphA2 levels are elevated in a significant fraction of the samples. Specific depletion of EphA2 in high-expressing melanoma cells using short hairpin RNA led to profound reductions in cellular viability, colony formation and migration in vitro and a dramatic loss of tumorigenic potential in vivo. Stable introduction of EphA2 into low-expressing cell lines enhanced proliferation, colony formation and migration, further supporting its pro-malignant phenotype. Interestingly, transient expression of EphA2 and/or Braf(V600E) in non-transformed melanocytes led to significant and additive apoptosis. These results verify that EphA2 is an important oncogene and potentially a common source of 'addiction' for many melanoma cells. Moreover, acute induction of EphA2 may purge genetically susceptible cells, thereby uncovering a more aggressive population that is in fact dependent on the oncogene.

Publication types

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

MeSH terms

  • Apoptosis / genetics
  • Apoptosis / radiation effects
  • Cell Line, Tumor
  • Cell Proliferation / radiation effects
  • Cell Survival
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Expression Regulation, Neoplastic / radiation effects
  • Gene Silencing
  • Humans
  • Melanoma / genetics
  • Melanoma / metabolism*
  • Melanoma / pathology
  • Oncogene Proteins / biosynthesis*
  • Oncogene Proteins / genetics
  • Receptor, EphA2 / biosynthesis*
  • Receptor, EphA2 / genetics
  • Ultraviolet Rays
  • Up-Regulation / genetics
  • Up-Regulation / radiation effects

Substances

  • Oncogene Proteins
  • Receptor, EphA2