KRAS, Hedgehog, Wnt and the Twisted Developmental Biology of Pancreatic Ductal Adenocarcinoma

Nat Rev Cancer. 2010 Oct;10(10):683-95. doi: 10.1038/nrc2899. Epub 2010 Sep 3.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is characterized by near-universal mutations in KRAS and frequent deregulation of crucial embryonic signalling pathways, including the Hedgehog (Hh) and Wnt-β-catenin cascades. The creation of mouse models that closely resemble the human disease has provided a platform to better understand when and in which cell types these pathways are misregulated during PDAC development. Here we examine the central part that KRAS plays in the biology of PDAC, and how the timing and location of Hh and Wnt-β-catenin signalling dictate the specification and oncogenic properties of PDAC.

Publication types

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

MeSH terms

  • Animals
  • Carcinoma, Pancreatic Ductal / genetics*
  • Carcinoma, Pancreatic Ductal / pathology
  • Cell Lineage
  • Genes, ras*
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / metabolism*
  • Humans
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology
  • Signal Transduction
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism*
  • beta Catenin / metabolism

Substances

  • Hedgehog Proteins
  • Wnt Proteins
  • beta Catenin