Author/Authors :
Ito، نويسنده , , Kosei and Lim، نويسنده , , Anthony Chee-Beng and Salto-Tellez، نويسنده , , Manuel and Motoda، نويسنده , , Lena and Osato، نويسنده , , Motomi and Chuang، نويسنده , , Linda Shyue Huey and Lee، نويسنده , , Cecilia Wei Lin and Voon، نويسنده , , Dominic Chih-Cheng and Koo، نويسنده , , Jason Kin Wai and Wang، نويسنده , , Huajing and Fukamachi، نويسنده , , Hiroshi and Ito، نويسنده , , Yoshiaki، نويسنده ,
Abstract :
Summary
estinal 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.
