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

Cell Cycle. 2009 Feb 1;8(3):383-90. doi: 10.4161/cc.8.3.7542. Epub 2009 Feb 3.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism
  • Epigenesis, Genetic*
  • Humans
  • Insulin-Like Growth Factor II / genetics
  • Insulin-Like Growth Factor II / metabolism
  • Neoplasms* / genetics
  • Neoplasms* / metabolism
  • Signal Transduction / physiology*
  • Wnt Proteins / metabolism
  • beta Catenin / metabolism


  • Wnt Proteins
  • beta Catenin
  • Insulin-Like Growth Factor II