E2F1 apoptosis counterattacked: evil strikes back

Trends Mol Med. 2013 Feb;19(2):89-98. doi: 10.1016/j.molmed.2012.10.009. Epub 2012 Dec 5.


Resistance to genotoxic drugs is the major cause of cancer therapy failure. In the past, E2F1 was recognized as a key regulator of apoptosis, but the latest evidence reveals that this transcription factor is aberrantly high in late-stage cancers and instead of apoptosis promotes tumor invasion and metastasis. This newly discovered activity of deregulated E2F1 reflects a cell context-dependent loss of its death-inducing function. We highlight the role of E2F1 in drug resistance by focusing on recent advances in elucidating the molecular mechanisms that counteract E2F1-induced apoptosis signaling in damaged cells. These mechanisms explain the paradox of high E2F1 expression in advanced tumors, highlight potential loopholes for cancers to escape from conventional treatment, and imply novel therapeutic strategies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis* / genetics
  • DNA Repair
  • Drug Resistance, Neoplasm
  • E2F1 Transcription Factor / genetics
  • E2F1 Transcription Factor / metabolism*
  • Humans
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Protein Binding
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Signal Transduction
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism


  • E2F1 Transcription Factor
  • Repressor Proteins
  • Tumor Suppressor Protein p53