A new link between epigenetic progenitor lesions in cancer and the dynamics of signal transduction

Winston Timp, Andre Levchenko, Andrew P. Feinberg

Research output: Contribution to journalReview articlepeer-review

Abstract

Our recent study of the mechanism by which an epigenetic alteration, loss of imprinting (LOI) of Igf2, increases tumor risk, revealed a strong relationship between IGF2 dosage, the dynamics of signaling along the IGF2 axis, cell proliferation and tumor risk.1 Colon epithelia in a mouse model with LOI of Igf2 showed increased sensitivity to IGF1R blockade and abrogation of premalignant lesion development in LOI(+) mice. These results are consistent with the epigenetic progenitor model of cancer,2 in which epigenetic changes precede and heighten risk of cancer in response to oncogenic mutations. Thus, one can envision a highly targeted and focused chemoprevention strategy targeted to signaling pathways in nonmalignant cells that have undergone an epigenetic lesion, rather than a broad approach toward reversing epigenetic lesions that may have unintended consequences affecting the whole epigenome.

Original languageEnglish (US)
Pages (from-to)383-390
Number of pages8
JournalCell Cycle
Volume8
Issue number3
DOIs
StatePublished - Feb 1 2009

Keywords

  • Colorectal cancer
  • Epigenetic progenitor model
  • Epigenetics
  • Imprinting
  • Signal transduction

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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