RUNX3 Attenuates β-Catenin/T Cell Factors in Intestinal Tumorigenesis
Copyright policy )RUNX3 Attenuates β-Catenin/T Cell Factors in Intestinal Tumorigenesis
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.
- National University of Singapore Singapore
- Nagasaki University Japan
- Nagasaki University Japan
- NAGASAKI UNIVERSITY
- Agency for Science, Technology and Research Singapore
Cancer Research, Adenomatous Polyposis Coli Protein, Blotting, Western, 610, name=Cancer Research, CELLCYCLE, name=Cell Biology, Adenomatous Polyps, Mice, Cell Line, Tumor, Cyclin D, Cyclins, Intestinal Neoplasms, Animals, Humans, Intestinal Mucosa, Mice, Knockout, Mice, Inbred BALB C, Hyperplasia, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, name=Oncology, Cell Biology, HCT116 Cells, name=SDG 3 - Good Health and Well-being, Intestines, Mice, Inbred C57BL, /dk/atira/pure/subjectarea/asjc/2700/2730, Core Binding Factor Alpha 3 Subunit, Oncology, SIGNALING, /dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being, /dk/atira/pure/subjectarea/asjc/1300/1306, Colorectal Neoplasms, /dk/atira/pure/subjectarea/asjc/1300/1307
Cancer Research, Adenomatous Polyposis Coli Protein, Blotting, Western, 610, name=Cancer Research, CELLCYCLE, name=Cell Biology, Adenomatous Polyps, Mice, Cell Line, Tumor, Cyclin D, Cyclins, Intestinal Neoplasms, Animals, Humans, Intestinal Mucosa, Mice, Knockout, Mice, Inbred BALB C, Hyperplasia, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, name=Oncology, Cell Biology, HCT116 Cells, name=SDG 3 - Good Health and Well-being, Intestines, Mice, Inbred C57BL, /dk/atira/pure/subjectarea/asjc/2700/2730, Core Binding Factor Alpha 3 Subunit, Oncology, SIGNALING, /dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being, /dk/atira/pure/subjectarea/asjc/1300/1306, Colorectal Neoplasms, /dk/atira/pure/subjectarea/asjc/1300/1307
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