Mechanistic study of EZH2 regulating β-catenin through AKT phosphorylation in colon cancer cell proliferation,mi-gration and invasion
Zhou Meng
Zhu Lei
Ju Jiyu
Yue Qi'an
Ji Wansheng
Abstract：Objective To explore the role of the AKT-EZH2-β-catenin axis in regulating the proliferation,migration,and invasion of colon cancer.Methods The expression levels of EZH2 in colon cancer tissues and SW480 colon cancer cells were analyzed using the GEPIA tool based on TCGA and GTEx databases and verified by Western blot(WB).The interaction among AKT phosphorylation,EZH2,and β-catenin was further investigated by co-immunoprecipitation(Co-IP)experiments.The effects of the AKT-EZH2-β-catenin axis on the proliferation,migration,and invasion of SW480 colon cancer cells were detected by 5-ethynyl-2'-deoxyuridine(EdU)assay,wound healing assay,and Transwell assay.Results The results of GEPIA and WB showed that the expression of EZH2 in colon cancer tissues and SW480 colon cancer cells was significantly higher than that in normal tissues and the human colonic epithelial cell line NCM460(P＜0.05).The Co-IP experimental results indicated that after AKT phosphorylation was activated by H2O2,the expression of pS473-AKT increased significantly(P＜0.05),and both AKT and EZH2 proteins were present in the precipitation complex.The results of the EdU assay,wound heal-ing assay,and Transwell assay showed that after AKT phosphorylation was activated by H2O2,the proliferation,migration,and invasion abilities of SW480 cells were significantly enhanced(P＜0.05).After silencing EZH2,the migration and invasion abilities of the cells were significantly decreased(P＜0.05).When β-catenin was further silenced,this inhibitory effect became more prominent.Conclusion There is an interaction among AKT,EZH2,and β-catenin.The high expression of EZH2 may phosphorylate AKT,thereby upregulating the expression and activity of β-catenin,and ultimately promoting the proliferation,migration,and invasion of colon cancer cells.
Keywords：Colon cancerEZH2AKTβ-cateninProliferationMigrationInvasionMechanism
Publication Date：2026-02-18
Online Publishing Date：2026-03-18(First online date of this platform, not the publication date of the document)
Pages：7( 220-225,242 )