Self-renewal and cancer of the gut: two sides of a coin

Science. 2005 Mar 25;307(5717):1904-9. doi: 10.1126/science.1104815.

Abstract

The intestinal epithelium follows the paradigms of stem cell biology established for other self-renewing tissues. With a unique topology, it constitutes a two-dimensional structure folded into valleys and hills: the proliferative crypts and the differentiated villi. Its unprecedented self-renewal rate appears reflected in a high susceptibility to malignant transformation. The molecular mechanisms that control homeostatic self-renewal and those that underlie colorectal cancer are remarkably symmetrical. Here, we discuss the biology of the intestinal epithelium, emphasizing the roles played by Wnt, bone morphogenic protein, and Notch signaling cascades in epithelial self-renewal and cancer.

Publication types

  • Review

MeSH terms

  • Adenomatous Polyposis Coli / genetics
  • Adenomatous Polyposis Coli / metabolism
  • Adenomatous Polyposis Coli / pathology
  • Animals
  • Bone Morphogenetic Proteins / metabolism
  • Cell Transformation, Neoplastic
  • Colorectal Neoplasms / etiology*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / physiopathology
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics
  • Colorectal Neoplasms, Hereditary Nonpolyposis / metabolism
  • Colorectal Neoplasms, Hereditary Nonpolyposis / pathology
  • Helix-Loop-Helix Motifs
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Intestinal Mucosa / cytology*
  • Intestinal Mucosa / embryology
  • Intestinal Mucosa / physiology*
  • Membrane Proteins / metabolism
  • Mutation
  • Receptors, Notch
  • Signal Transduction
  • Stem Cells / cytology
  • Stem Cells / physiology
  • Wnt Proteins

Substances

  • Bone Morphogenetic Proteins
  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Receptors, Notch
  • Wnt Proteins