E2F1 in melanoma progression and metastasis

J Natl Cancer Inst. 2010 Jan 20;102(2):127-33. doi: 10.1093/jnci/djp458. Epub 2009 Dec 21.


Metastases are responsible for cancer deaths, but the molecular alterations leading to tumor progression are unclear. Overexpression of the E2F1 transcription factor is common in high-grade tumors that are associated with poor patient survival. To investigate the association of enhanced E2F1 activity with aggressive phenotype, we performed a gene-specific silencing approach in a metastatic melanoma model. Knockdown of endogenous E2F1 via E2F1 small hairpin RNA (shRNA) expression increased E-cadherin expression of metastatic SK-Mel-147 melanoma cells and reduced their invasive potential but not their proliferative activity. Although growth rates of SK-Mel-147 and SK-Mel-103 xenograft tumors expressing E2F1 shRNA or control shRNA were similar, mice implanted with cells expressing E2F1 shRNA had a smaller area of metastases per lung than control mice (n = 3 mice per group; 5% vs 46%, difference = 41%, 95% confidence interval = 15% to 67%; P = .01; one-way analysis of variance). We identified epidermal growth factor receptor as a direct target of E2F1 and demonstrated that inhibition of receptor signaling abrogates E2F1-induced invasiveness, emphasizing the importance of the E2F1-epidermal growth factor receptor interaction as a driving force in melanoma progression that may serve as a paradigm for E2F1-induced metastasis in other human cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Disease Progression
  • E2F1 Transcription Factor / metabolism*
  • ErbB Receptors / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Melanoma / metabolism
  • Melanoma / secondary*
  • Neoplasm Invasiveness
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology*


  • E2F1 Transcription Factor
  • E2F1 protein, human
  • ErbB Receptors