Transcriptional enhanced associate domain (TEAD) transcription factors play important
roles during development, cell proliferation, regeneration, and tissue homeostasis. TEAD integrates
with and coordinates various signal transduction pathways, including Hippo, Wnt, transforming
growth factor beta (TGFB), and epidermal growth factor receptor (EGFR) pathways. TEAD
deregulation affects well-established cancer genes such as KRAS, BRAF, LKB1, NF2, and MYC,
and its transcriptional output plays an important role in tumor progression, metastasis, cancer
metabolism, immunity, and drug resistance. To date, TEADs have been recognized to be key
transcription factors of the Hippo pathway. Therefore, most studies are focused on the Hippo kinases
and YAP/TAZ, whereas the Hippo-dependent and Hippo-independent regulators and regulations
governing TEAD have only emerged recently. Deregulation of the TEAD transcriptional output plays
an important rolesrole in tumor progression and serves as a prognostic biomarker due to a high correlation
with clinicopathological parameters in human malignancies. In addition, discovering the molecular
mechanisms of TEAD, such as post-translational modifications and nucleocytoplasmic shuttling,
represents an important means of modulating TEAD transcriptional activity. Collectively, this review
highlights the role of TEAD in multistep-tumorigenesis by interacting with upstream oncogenic
signaling pathways and controlling downstream target genes, which provides unprecedented insight
and rationale into developing TEAD-targeted anticancer therapeutics.