From fly wings to targeted cancer therapies: a centennial for notch signaling

Cancer Cell. 2014 Mar 17;25(3):318-34. doi: 10.1016/j.ccr.2014.02.018.

Abstract

Since Notch phenotypes in Drosophila melanogaster were first identified 100 years ago, Notch signaling has been extensively characterized as a regulator of cell-fate decisions in a variety of organisms and tissues. However, in the past 20 years, accumulating evidence has linked alterations in the Notch pathway to tumorigenesis. In this review, we discuss the protumorigenic and tumor-suppressive functions of Notch signaling, and dissect the molecular mechanisms that underlie these functions in hematopoietic cancers and solid tumors. Finally, we link these mechanisms and observations to possible therapeutic strategies targeting the Notch pathway in human cancers.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism*
  • Drosophila melanogaster / genetics
  • Humans
  • Immunoglobulin J Recombination Signal Sequence-Binding Protein / metabolism
  • Neoplasms / drug therapy
  • Neoplasms / metabolism*
  • Receptors, Notch / antagonists & inhibitors
  • Receptors, Notch / genetics*
  • Receptors, Notch / metabolism*
  • Signal Transduction / genetics

Substances

  • Immunoglobulin J Recombination Signal Sequence-Binding Protein
  • RBPJ protein, human
  • Receptors, Notch