Sox4 functions as a positive regulator of beta-catenin signaling through upregulation of TCF4 during morular differentiation of endometrial carcinomas

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In endometrial carcinoma (EmCa) cells, Sox4 could enhance beta-catenin/TCF4 transcription, through up-regulation of TCF4 at the transcription level, without any direct beta-catenin association. Cells stably overexpressing Sox4 showed significant decreases in proliferation rate, along with increases in expression of p21waf1, in contrast to increased cell growth observed with knockdown. Sox7 could transcriptionally up-regulate Sox4 expression. Finally, Sox4 immunoreactivity was frequently pronounced in morules of Em Cas, the expression being positively correlated with status of beta-catenin, TCF4, and Sox7, and inversely with cell proliferation. These data therefore suggest that Sox4 may serve as a positive regulator of beta-catenin signaling through alteration in TCF4 expression during morular differentiation of Em Ca cells, leading to inhibition of cell proliferation.