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Science 25 March 2005:
Vol. 307. no. 5717, pp. 1904 - 1909
DOI: 10.1126/science.1104815

Review

Self-Renewal and Cancer of the Gut: Two Sides of a Coin

Freddy Radtke1 and Hans Clevers2*

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.

1 Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Chemin de Boveresses 155, CH-1066 Epalinges, Switzerland.
2 Hubrecht Institute, Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584CT Utrecht, Netherlands.

* To whom correspondence should be addressed. E-mail: clevers{at}niob.knaw.nl

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Science. ISSN 0036-8075 (print), 1095-9203 (online)