RUNX3 attenuates beta-catenin/T cell factors in intestinal tumorigenesis.

نویسندگان

  • Kosei Ito
  • Anthony Chee-Beng Lim
  • Manuel Salto-Tellez
  • Lena Motoda
  • Motomi Osato
  • Linda Shyue Huey Chuang
  • Cecilia Wei Lin Lee
  • Dominic Chih-Cheng Voon
  • Jason Kin Wai Koo
  • Huajing Wang
  • Hiroshi Fukamachi
  • Yoshiaki Ito
چکیده

In intestinal epithelial cells, inactivation of APC, a key regulator of the Wnt pathway, activates beta-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 beta-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 beta-catenin accumulation, indicating that RUNX3 inactivation independently induces intestinal adenomas. In human colon cancers, RUNX3 is frequently inactivated with concomitant beta-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.

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عنوان ژورنال:
  • Cancer cell

دوره 14 3  شماره 

صفحات  -

تاریخ انتشار 2008