Tead2 expression levels control Yap/Taz subcellular distribution, zyxin expression, and epithelial-mesenchymal transition

Abstract

The cellular changes during an epithelial-mesenchymal transition (EMT) largely rely on global changes in gene expression orchestrated by transcription factors. Tead transcription factors and their transcriptional co-activators Yap and Taz have been previously implicated in promoting an EMT, however, their direct transcriptional target genes and their functional role during EMT have remained widely elusive. We have uncovered a previously unanticipated role of the transcription factor Tead2 during EMT. During EMT in mammary gland epithelial cells and breast cancer cells, levels of Tead2 increase in the nucleus of cells, thereby directing a predominant nuclear localization of its co-factors Yap and Taz via the formation of Tead2/Yap/Taz complexes. Genome-wide chromatin immunoprecipitation/next generation sequencing in combination with gene expression profiling reveals the transcriptional targets of Tead2 during EMT. Among these, zyxin contributes to the migratory and invasive phenotype evoked by Tead2. The results demonstrate that Tead transcription factors are critical regulators of Yap/Taz cellular distribution and together they control the expression of genes critical for EMT and metastasis.