Self-renewal and cancer of the gut: two sides of a coin.
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.
Radtke
Freddy
F
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Chemin de Boveresses 155, CH-1066 Epalinges, Switzerland.
Clevers
Hans
H
D011125:Adenomatous Polyposis Coli / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002471:Cell Transformation, Neoplastic; D015179:Colorectal Neoplasms / Q000209:etiology* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology* / Q000196:embryology / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D009154:Mutation; D051880:Receptors, Notch; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D051153:Wnt Proteins
D019485:Bone Morphogenetic Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051880:Receptors, Notch; D051153:Wnt Proteins