Transcriptional Regulation of the Hippo Pathway: Current Understanding and Insights from Single-Cell Technologies

Abstract

The Hippo pathway regulates tissue homeostasis in normal development and drives oncogenic processes. In this review, we extensively discuss how YAP/TAZ/TEAD cooperate with other master transcription factors and epigenetic cofactors to orchestrate a broad spectrum of transcriptional responses. Even though these responses are often context- and lineage-specific, we do not have a good understanding of how such precise and specific transcriptional control is achieved—whether they are driven by differences in TEAD paralogs, or recruitment of cofactors to tissue-specific enhancers. We believe that emerging single-cell technologies would enable a granular understanding of how the Hippo pathway influences cell fate and drives oncogenic processes, ultimately allowing us to design better pharmacological agents against TEADs and identify robust pharmacodynamics markers of Hippo pathway inhibition.

Chromatin Remodelling Molecule ARID1A Determines Metastatic Heterogeneity in Triple-Negative Breast Cancer by Competitively Binding to YAP

“…We found that knockout of ARID1A reduced YAP/BRG1 binding, whereas reduced BRG1 expression had no significant effect on ARID1A/YAP binding (Figure 6E), suggesting that ARID1A plays an important role in the formation of the YAP/BRG1 complex. YAP, which is present in the nucleus, can bind to TEAD to form a complex that activates the expression of its downstream genes, thereby promoting tumour development [13,14]. When the expression of ARID1A is inhibited, YAP dissociated from the compound and bound to TEAD (Figure 6F).…”

Atypical Macropinocytosis Contributes to Malignant Progression: A Review of Recent Evidence in Endometrioid Endometrial Cancer Cells

“…In LSR-knockdown Sawano cells, dobutamine treatment suppressed the enhancement of cell motility and invasion, associated with an increase in the amount of phosphorylated YAP [ 77 ]. Activation of the transcription factor TEAD by YAP increased the expression of genes associated with cell proliferation and survival [ 81 ]. LSR-knockdown Sawano cells induce expression of the Hippo pathway transcription factor TEAD and inducible gene amphiregulin (AREG) [ 77 ].…”

The Hippo signalling pathway and its impact on eye diseases

“…2 The key effector proteins of the mammalian Hippo signalling pathway, yes-associated protein (YAP) and transcriptional coactivator with a PDZ-binding motif (TAZ), collectively known as YAP/TAZ, regulate cell fate decisions. 3 Activation of the canonical Hippo pathway leads to the formation of the sterility 20-like protein kinase (MST1/2) and Salvador 1 (SAV1) complex, which subsequently phosphorylates the large tumour suppressor (LATS1/2) and MOB kinase activator 1 (MOB1). The activated LATS1/2-MOB1 complex, in turn, phosphorylates YAP/TAZ, resulting in YAP/TAZ retention and degradation in the cytoplasm, thereby preventing their accumulation in the nucleus and downstream gene expression.…”

“…The Hippo signalling pathway is an evolutionarily conserved pathway that plays an integral role in regulating glucose metabolism, 1 cellular proliferation, fate regulation, apoptosis, and control of tissue growth and regeneration 2 . The key effector proteins of the mammalian Hippo signalling pathway, yes‐associated protein (YAP) and transcriptional coactivator with a PDZ‐binding motif (TAZ), collectively known as YAP/TAZ, regulate cell fate decisions 3 . Activation of the canonical Hippo pathway leads to the formation of the sterility 20‐like protein kinase (MST1/2) and Salvador 1 (SAV1) complex, which subsequently phosphorylates the large tumour suppressor (LATS1/2) and MOB kinase activator 1 (MOB1).…”