Cancer Biology

Responding to R-Spondin

Science's STKE  23 Aug 2005:
Vol. 2005, Issue 298, pp. tw307
DOI: 10.1126/stke.2982005tw307

Intestinal epithelial integrity in the gut is maintained through a delicate balance between rapid cellular proliferation, differentiation, and cell death, regulated by the Wnt/β-catenin signaling pathway. Kim et al. provide evidence that a recently identified human orphan growth factor exerts a strong influence on how the β-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 β-catenin by the Wnt protein, which suggests that another pathway may also influence β-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.

K.-A. Kim, M. Kakitani, J. Zhao, T. Oshima, T. Tang, M. Binnerts, Y. Liu, B. Boyle, E. Park, P. Emtage, W. D. Funk, K. Tomizuka, Mitogenic influence of human R-spondin1 on the intestinal epithelium. Science 309, 1256-1259 (2005). [Abstract] [Full Text]