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Science 19 August 2005:
Vol. 309. no. 5738, p. 1149
DOI: 10.1126/science.309.5738.1149o
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Intestinal epithelial integrity in the gut is maintained through a delicate balance between rapid cellular proliferation, differentiation, and cell death, regulated by the Wnt/beta-catenin signaling pathway. Kim et al. (p. 1256) provide evidence that a recently identified human orphan growth factor exerts a strong influence on how the beta-catenin pathway regulates epithelial cell proliferation. Using an in vivo screening system, the authors found that R-spondin1 could act as a growth factor to increase crypt epithelial cell proliferation, leading to thickening and elongation of the small and large intestine. Unexpectedly, this effect appeared to operate independently of conventional stabilization of beta-catenin by the Wnt protein, suggesting that another pathway may also influence beta-catenin-dependent gene regulation. In a gut tumor treatment model, R-spondin1 reduced the strong cytotoxicity associated with a chemotherapeutic agent without impeding tumor growth.




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