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: It has previously been shown that RUNX3 binds to TCF4/β-catenin complex, which suppresses the binding of the complex to the Wnt target gene promoters.(12,13) Notably, immunoprecipitation experiments revealed that RUNX3 bound β-catenin and TCF4 also in the RUNX3-transfected KatoIII cells (Fig. 5a), suggesting that RUNX3, TCF4 and β-catenin form a ternary complex also in KatoIII cells.
Affiliation: Division of Genetics, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.