RUNX3 Attenuates β-Catenin/T Cell Factors in Intestinal Tumorigenesis

Abstract

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.