In intestinal epithelial cells, inactivation of APC, a key regulator of the Wnt pathway, activates β-catenin to initiate tumorigenesis. However, other alterations may be involved in intestinal tumorigenesis. Here we found that RUNX3, a gastric tumor suppressor, forms a ternary complex with β-catenin/TCF4 and attenuates Wnt signaling activity. A significant fraction of human sporadic colorectal adenomas and Runx3+/- mouse intestinal adenomas showed inactivation of RUNX3 without apparent β-catenin accumulation, indicating that RUNX3 inactivation independently induces intestinal adenomas. In human colon cancers, RUNX3 is frequently inactivated with concomitant β-catenin accumulation, suggesting that adenomas induced by inactivation of RUNX3 may progress to malignancy. Taken together, these data demonstrate that RUNX3 functions as a tumor suppressor by attenuating Wnt signaling. © 2008 Elsevier Inc. All rights reserved.
Ito, K., Lim, A. C. B., Salto-Tellez, M., Motoda, L., Osato, M., Chuang, L. S. H., … Ito, Y. (2008). RUNX3 Attenuates β-Catenin/T Cell Factors in Intestinal Tumorigenesis. Cancer Cell, 14(3), 226–237. https://doi.org/10.1016/j.ccr.2008.08.004