Epha2 is a critical oncogene in melanoma

D. Udayakumar, G. Zhang, Z. Ji, C. N. Njauw, P. Mroz, H. Tsao

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4921-4929
Number of pages9
JournalOncogene
Volume30
Issue number50
DOIs
StatePublished - Dec 15 2011

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health (1R21ES013964; HT), the Dermatology Foundation (DU), the American Skin Association (HT and DU), the Melanoma Research Alliance (to HT) and the generous philanthropic donors at MGH. We thank Dr Jie Zhao and other members of the Wellman Center Pathology core facility for their help with the tissue sections and confocal analysis. We also thank Dr Michael Hamblin for his support in mice tumor studies.

Keywords

  • EphA2
  • melanoma
  • survival

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