The TEAD family of transcription factors are the final nuclear effectors of the Hippo pathway,
which regulate cell growth, proliferation, and tissue homeostasis via their transcriptional target genes.
Since their initial discovery three decades ago, TEADs have been best studied in the context of the
Hippo-YAP/TAZ signaling pathway and tumorigenesis. To date, studies on TEAD activity are limited
to serving as the functional readout of the Hippo-YAP/TAZ pathway. However, recent evidence
suggests that nucleocytoplasmic shuttling, post-translational modifications, and crosstalk between
oncogenic signaling pathways are important determinants of TEAD activity both in vitro and in vivo.
Importantly, since the Hippo pathway components are hardly druggable, TEADs have emerged
as critical drug candidates to treat human diseases including cancer, cardiovascular diseases, and
neurodegenerative disorders. The current review underscores and reinterprets the oncogenic role of
TEADs in tumorigenesis in past reports from a TEAD point of view in order to provide unprecedented
insight and rationale into developing TEAD-targeted anticancer therapeutics.