A Non-canonical Role of YAP/TEAD Is Required for Activation of Estrogen-Regulated Enhancers in Breast Cancer

Zhu, Ce; Li, Li; Zhang, Zhao; Bi, Mingjun; Wang, Hu; Su, Wenyue; Hernandez, Karen; Li, Pingping; Chen, Junqiang; Chen, Mingqiu; Huang, Tim Hui-Ming; Chen, Lizhen; Liu, Zhijie

doi:10.1016/j.molcel.2019.06.010

Cited by 102 publications

(80 citation statements)

References 60 publications

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“…AIB1 and the related p160 co-activators NCOA-1 and NCOA-2 interact with nuclear hormone receptors (e.g., estrogen and androgen receptors-ER and AR) that would, in turn, seem to be candidate Hippointeracting factors. Indeed, a recent paper [9] supports a model of YAP-ER crosstalk by a mechanism that resembles that proposed by Kushner et al (Fig 1B, left panel). This study found YAP-TEAD bind directly to ER and are required for estrogen-induced gene transcription and breast cancer growth.…”

supporting

confidence: 80%

One repressor to rule them all: ANCO1 links YAP and AIB1

Zhang

Moberg

2019

EMBO Reports

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The transcriptional co-activators YAP and AIB1 individually promote breast cancer progression, but are not known to be mechanistically linked. A study published in this issue of EMBO Reports [1] now shows that YAP-AIB1 form a physical complex in breast epithelial cells that cooperates in both activation and, unexpectedly, repression of key breast cancer genes. The repressive effect is due to the recruitment of ANCO1, a previously defined AIB1 interactor [2] that binds and inhibits the YAP-AIB1 complex. These data identify ANCO1 as a candidate tumor suppressor through YAP-AIB1 inhibition and could hint at a broader crosstalk between pathways that utilize YAP and AIB1 to control epithelial homeostasis.EMBO Reports (2020) 21: e49647

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supporting

confidence: 80%

One repressor to rule them all: ANCO1 links YAP and AIB1

Zhang

Moberg

2019

EMBO Reports

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“…45 The YAP-TEAD4 complex co-regulates ERα for estrogen-regulated enhancer activation, indicating that a non-canonical TEAD4 mechanism is responsible for breast cancer growth. 10 On the other hand, activator protein-1 (AP-1, a dimer of JUN and FOS) is a transcription factor and proto-oncogene. 46 By ChIP-seq analysis, AP-1 was demonstrated to co-occupy chromatin with the TEAD-YAP/TAZ complex and to promote breast cancer cell proliferation.…”

Section: Cooperation With Transcription Factorsmentioning

confidence: 99%

“…TEAD4 is highly expressed in skeletal muscle, initial studies focused on its role in blastocyst formation 6 and reported that TEAD4 is required for specification of the trophectoderm lineage in preimplantation embryos. [6][7][8] Recently, TEAD4 was demonstrated to be a novel prognostic marker of gastric cancer, 9 breast cancer, 10 colorectal cancer, 11 melanoma, 12 laryngeal cancer, 13 and head-neck squamous cell carcinoma. 14 Apart from its role in the canonical Hippo-YAP/TAZ pathway, other studies have reported its participation in post-translational modifications, 9,15 crosstalk between cancer-related signaling pathways, 16 and cancer-causing mutations.…”

Section: Introductionmentioning

confidence: 99%

<p>Structural and Functional Overview of TEAD4 in Cancer Biology</p>

Chen¹,

Huang²,

Zhu³

et al. 2020

OTT

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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 Yesassociated 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.

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“…One explanation that would be consistent with both of these observations might be that the Yki/Sd complex does not bind to the enhancer directly but rather via a protein-protein interaction with a different DNAbinding protein such as Mad. Indeed, it has recently been shown that in mammalian cells, a complex containing YAP1 and the Sd ortholog TEAD4 can bind to enhancers of ecdysoneregulated genes not by interacting with DNA sequences, but rather via another protein, estrogen receptor α, that is already bound to the enhancer (Zhu et al, 2019). Recent studies also suggest a mechanism by which CtBP can function as a repressor of Sd-regulated genes.…”

Section: Regulation Of Ban By Ctbp Via the Hippo Pathwaymentioning

confidence: 99%

The transcriptional co-repressor CtBP is a negative regulator of growth that antagonizes the Yorkie and JNK/AP-1 pathways

Sumabat¹,

Worley²,

Pellock

et al. 2019

Preprint

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Multicellular organisms require strict growth control mechanisms to ensure that an organ reaches, but does not grossly exceed, its appropriate size and shape. In an unbiased mosaic screen for genes involved in growth regulation, we identified a loss-of-function allele of the gene CtBP that conferred a growth advantage to homozygous mutant tissue. CtBP encodes a transcriptional co-repressor found in diverse organisms, yet its role in regulating tissue growth is not known. We found that CtBP functions as a negative regulator of growth by restricting the expression of the growth-promoting microRNA bantam (ban). ban is a known target of the Hippo pathway effector Yorkie (Yki). We show that loss of CtBP function leads to the activation of a minimal enhancer of ban via both Yki-dependent and AP-1 transcription factor-dependent mechanisms. AP-1 is downstream of the Jun N-terminal Kinase (JNK) pathway and thus JNK could regulate growth during development via ban. Furthermore, we show that distinct isoforms of the AP-1 component Fos differ in their ability to activate this enhancer. Since the orthologous pathways in mammalian cells (YAP/TEAD and AP-1) converge on enhancers implicated in tumor progression, a role for mammalian CtBP proteins at those enhancers merits attention.

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A Non-canonical Role of YAP/TEAD Is Required for Activation of Estrogen-Regulated Enhancers in Breast Cancer

Cited by 102 publications

References 60 publications

One repressor to rule them all: ANCO1 links YAP and AIB1

One repressor to rule them all: ANCO1 links YAP and AIB1

<p>Structural and Functional Overview of TEAD4 in Cancer Biology</p>

The transcriptional co-repressor CtBP is a negative regulator of growth that antagonizes the Yorkie and JNK/AP-1 pathways

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