Context-dependent activation of Wnt signaling by tumor suppressor RUNX3 in gastric cancer cells.
Bottom Line: Here, we confirmed that RUNX3 suppressed Wnt signaling activity in several gastric cancer cell lines; however, we found that RUNX3 increased the Wnt signaling activity in KatoIII and SNU668 gastric cancer cells.As found previously, RUNX3 also binds to TCF4 and β-catenin in KatoIII cells, suggesting that these molecules form a ternary complex.These results indicate that RUNX3 can either suppress or activate the Wnt signaling pathway through its binding to the TCF4/β-catenin complex by cell context-dependent mechanisms.
Affiliation: Division of Genetics, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.Show MeSH
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Mentions: We further examined the RUNX3-induced Wnt activation mechanism using KatoIII cells. In KatoIII cells, Wnt signaling is activated by β-catenin gene amplification.(17) Treatment of control KatoIII cells with a Wnt ligand secretion inhibitor C59 significantly suppressed the endogenous Wnt signaling, indicating that Wnt ligand stimulation maintains the basal Wnt activation level (Fig. 2a). C59 treatment also decreased the luciferase activity in the RUNX3-expressing KatoIII cells. However, the ratio of the RUNX3-induced increase of luciferase activity in the C59-treated cells was similar to that in the control cells; that is, approximately 4.5-fold the control levels. Accordingly, it is possible that RUNX3 increases Wnt signaling activity in KatoIII cells through a ligand-independent mechanism.
Affiliation: Division of Genetics, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.