Structural and Functional Overview of TEAD4 in Cancer Biology

TEA domain transcription factor 4 (TEAD4) is an important member of the TEAD family. As a downstream effector of the Hippo pathway, TEAD4 has essential roles in cell proliferation, cell survival, tissue regeneration, and stem cell maintenance. TEAD4 contains a TEA DNA binding domain that binds the promoters of target genes and a Yes-associated protein/transcriptional co-activator with PDZ-binding motif (YAP/TAZ) binding domain that associates with transcriptional cofactors. TEAD4 coordinates with YAP, TAZ, VGLL, and other transcription factors to regulate different cellular processes in cancer via its transcriptional output. Moreover, TEAD4 undergoes post-translational modifications and subcellular translocations, and both processes have been shown to shed new insights on how TEAD transcriptional activity can be modified. In summary, TEAD4 has important roles in cancer, including epithelial–mesenchymal transition (EMT), metastasis, cancer stem cell dynamics, and chemotherapeutic drug resistance, suggesting that TEAD4 may be a promising prognostic biomarker in cancer.