Emerging roles of TEAD transcription factors and its coactivators in cancers

Abstract

TEAD proteins are transcription factors that are crucial for development, but also play a role in cancers. Several developmentally and pathologically important genes are upregulated by TEADs. TEADs have a TEA domain that enables them to bind specific DNA elements and a transactivation domain that enables them to interact with coactivators. TEADs on their own are unable to activate transcription and they require the help of coactivators. Several TEAD-interacting coactivators are known and they can be classified into three groups: (1) YAP and its paralog TAZ; (2) Vgll proteins; and (3) p160s. Accordingly, these coactivators also play a role in development and cancers. Recent studies have shown that TEADs and their coactivators aid in the progression of various cancers, including the difficult to treat glioblastoma, liver and ovarian cancers. They facilitate cancer progression through expression of proliferation promoting genes such as c-myc, survivin, Axl, CTGF and Cyr61. There is also a good correlation between high TEAD or its coactivator expression and poor prognosis in various cancers. Given the fact that TEADs and their coactivators need to work together for a functional outcome, disrupting the interaction between them appears to be a viable option for cancer therapy. Structures of TEAD-coactivator complexes have been elucidated and will facilitate drug design and development.

VGLL4 functions as a new tumor suppressor in lung cancer by negatively regulating the YAP-TEAD transcriptional complex

“…There are 4 VGLL proteins in mammals, named VGLL1-4. These proteins bear no sequence similarity except for the TDU domain (the TEAD-interacting domain) [24][25][26][27][28]. Previous studies showed that VGLL1 promotes cell proliferation and exhibits high expression in basal-like breast cancer [29,30].…”

JCAD Promotes Progression of Nonalcoholic Steatohepatitis to Liver Cancer by Inhibiting LATS2 Kinase Activity

“…YAP is transcriptionally active when it is translocated into the nucleus (19). The dephosphorylation of YAP promotes YAP nuclear translocation and upregulates the YAP/TEAD association, leading to YAP/TEAD transcriptional activation, and activates target gene (GLI2 and CCND1) expression (20,21).…”

CCN1 induces hepatic ductular reaction through integrin αvβ5–mediated activation of NF-κB

“…Liver tissue array (US Biomax Inc.) was Ccn1 is a growth factor-inducible immediate-early gene that is transcriptionally activated by a variety of stimuli (62). As a known target gene of the YAP transcriptional coactivator (63,64), Ccn1 may mediate some of the effects of the Hippo pathway. Recent studies have shown that deletion of YAP in the liver compromises ductular reaction after BDL with increased parenchymal necrosis (65), suggesting that impaired Ccn1 expression might have contributed to the observed phenotypes.…”