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

K. Ito, A.C.B. Lim, Manuel Salto-Tellez, L. Motoda, M. Osato, L. Shyue, H. Chuang, C.W.L. Lee, D.C.C. Voon, J.K.W. Koo, H.J. Wang, H. Fukamachi, Y. Ito

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163 Citations (Scopus)

Abstract

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/7CF4 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.
Original languageEnglish
Pages (from-to)226-237
Number of pages12
JournalCancer Cell
Volume14
Issue number3
DOIs
Publication statusPublished - 09 Sep 2008

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

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