EphA2 is a critical oncogene in melanoma.

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  • Author(s): Udayakumar D;Udayakumar D; Zhang G; Ji Z; Njauw CN; Mroz P; Tsao H
  • Source:
    Oncogene [Oncogene] 2011 Dec 15; Vol. 30 (50), pp. 4921-9. Date of Electronic Publication: 2011 Jun 13.
  • Publication Type:
    Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Nature Publishing Group Country of Publication: England NLM ID: 8711562 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5594 (Electronic) Linking ISSN: 09509232 NLM ISO Abbreviation: Oncogene Subsets: MEDLINE
    • Publication Information:
      Publication: <2002->: Basingstoke : Nature Publishing Group
      Original Publication: Basingstoke, Hampshire, UK : Scientific & Medical Division, MacMillan Press, c1987-
    • Subject Terms:
    • 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.
    • References:
      Prostate. 1999 Dec 1;41(4):275-80. (PMID: 10544301)
      Oncogene. 2003 May 19;22(20):3070-5. (PMID: 12789282)
      Int J Cancer. 1999 Oct 22;84(5):494-501. (PMID: 10502726)
      Cancer Res. 2009 Mar 1;69(5):2072-81. (PMID: 19244130)
      Nature. 2010 May 27;465(7297):492-6. (PMID: 20505730)
      Oncogene. 2001 Oct 4;20(45):6503-15. (PMID: 11641774)
      Am J Pathol. 2002 Mar;160(3):1009-19. (PMID: 11891198)
      Gynecol Oncol. 2005 Nov;99(2):278-86. (PMID: 16061279)
      J Invest Dermatol. 2005 Dec;125(6):1242-51. (PMID: 16354195)
      Mol Biol Cell. 2009 May;20(10):2572-81. (PMID: 19321667)
      Genomics. 1997 Mar 1;40(2):371-4. (PMID: 9119409)
      Cancer Res. 2004 Apr 1;64(7):2338-42. (PMID: 15059882)
      Mech Dev. 1994 May;46(2):87-100. (PMID: 7918100)
      J Invest Dermatol. 2006 Nov;126(11):2490-506. (PMID: 16888633)
      Cancer. 2009 Jun 15;115(12):2684-92. (PMID: 19396818)
      J Invest Dermatol. 2004 Feb;122(2):337-41. (PMID: 15009714)
      Int J Cancer. 2009 Mar 15;124(6):1366-71. (PMID: 19089910)
      Am J Pathol. 2003 Apr;162(4):1037-42. (PMID: 12651595)
      Int J Cancer. 2003 Feb 20;103(5):657-63. (PMID: 12494475)
      J Cancer Res Clin Oncol. 2011 May;137(5):761-9. (PMID: 20614133)
      Pathobiology. 1997;65(4):195-203. (PMID: 9396043)
      Int J Cancer. 2010 Feb 15;126(4):940-9. (PMID: 19642143)
      Cancer Res. 1987 Jun 15;47(12):3239-45. (PMID: 2438036)
      Methods. 2003 Jul;30(3):256-68. (PMID: 12798140)
      Cancer Biol Ther. 2009 Feb;8(3):279-88. (PMID: 19223760)
      BMC Cancer. 2006 Jun 01;6:144. (PMID: 16737551)
      Nat Protoc. 2007;2(2):329-33. (PMID: 17406593)
      Am J Pathol. 2009 Apr;174(4):1492-503. (PMID: 19264906)
      Cancer Biol Ther. 2008 Jul;7(7):1098-103. (PMID: 18443431)
      Cancer Res. 2008 Mar 15;68(6):1691-6. (PMID: 18339848)
      Crit Rev Oncol Hematol. 2002 Oct;44(1):17-27. (PMID: 12398997)
      Dev Dyn. 2007 Jul;236(7):1997-2003. (PMID: 17576135)
      Oncogene. 2008 May 1;27(20):2934-40. (PMID: 18059341)
      Cancer Res. 2003 Sep 1;63(17):5198-202. (PMID: 14500344)
      Cell. 2008 Feb 8;132(3):363-74. (PMID: 18267069)
      Oncogene. 1994 May;9(5):1461-7. (PMID: 8152808)
      Oncogene. 1994 Jun;9(6):1613-24. (PMID: 8183555)
      Cancer Res. 2001 Mar 1;61(5):2301-6. (PMID: 11280802)
      Cancer Biol Ther. 2006 Feb;5(2):228-33. (PMID: 16481735)
      Cancer Sci. 2004 Feb;95(2):136-41. (PMID: 14965363)
      Cancer Cell. 2009 Jul 7;16(1):9-20. (PMID: 19573808)
      Dev Biol. 1998 Jan 1;193(1):21-35. (PMID: 9466885)
    • Grant Information:
      R21 ES013964 United States ES NIEHS NIH HHS; R21 ES013964-02 United States ES NIEHS NIH HHS; 1R21ES013964 United States ES NIEHS NIH HHS
    • Accession Number:
      0 (Oncogene Proteins)
      EC 2.7.10.1 (Receptor, EphA2)
    • Publication Date:
      Date Created: 20110614 Date Completed: 20120202 Latest Revision: 20211020
    • Publication Date:
      20221213
    • Accession Number:
      PMC3175290
    • Accession Number:
      10.1038/onc.2011.210
    • Accession Number:
      21666714