Evidence map›Paper›PMID 35217640›Full record

ArticleNature communications2022

Transcriptional repression of estrogen receptor alpha by YAP reveals the Hippo pathway as therapeutic target for ER

Shenghong Ma, Tracy Tang, Gary Probst, Andrei Konradi, Chunyu Jin, Fulong Li, J Silvio Gutkind, Xiang-Dong Fu, Kun-Liang Guan

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
93citing papers in PubMed, 1 pooled it
14.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

93 citing papers in PubMed, 1 synthesis or guideline pooled it, 132 citations in OpenAlex.

  1. Pooled it
  2. PROTACs in cancer therapy: targeted degradation of GPX4, PARP and epigenetic regulators.Journal of enzyme inhibition and medicinal chemistry · 2026
    Review
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. Review
  20. Article

33 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Shenghong MaDepartment of Pharmacology and Moores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA.ORCID http://orcid.org/0000-0002-6335-7715
Tracy TangVivace Therapeutics, San Mateo, CA, 94403, USA.
Gary ProbstVivace Therapeutics, San Mateo, CA, 94403, USA.
Andrei KonradiVivace Therapeutics, San Mateo, CA, 94403, USA.
Chunyu JinHoward Hughes Medical Institute, Department of Medicine, University of California San Diego, La Jolla, CA, 92093, USA.
Fulong LiDepartment of Pharmacology and Moores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA.
J Silvio GutkindDepartment of Pharmacology and Moores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA.
Xiang-Dong FuDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, 92093, USA.ORCID http://orcid.org/0000-0001-5499-8732
Kun-Liang GuanDepartment of Pharmacology and Moores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA. kuguan@ucsd.edu.ORCID http://orcid.org/0000-0003-1892-0174
University of California San Diego · USMateon Therapeutics (United States) · USHoward Hughes Medical Institute · US

Funding

PROTEIN PHOSPHORYLATION AND GROWTH FACTOR FUNCTIONR01GM051586 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BROWN, JOAN HELLER · 1994 to 2024
$7.9M
The mTOR and Hippo pathway in cell growth and cancerR35CA196878 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GUAN, KUN-LIANG · 2015 to 2019
$4.0M
Molecular Mechanism and Therapy for Ocular MelanomaR01CA217642 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BROWN, JOAN HELLER · 2017 to 2022
$2.4M
Functional interplay between Hippo and estrogen receptor ESR1R01CA268179 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jing Yang · 2022 to 2026
$2.1M
NCI NIH HHS R01 CA217642NCI NIH HHS R01 CA268179NCI NIH HHS R35 CA196878NIGMS NIH HHS R01 GM051586
6 · The paper itself

Abstract

Extensive knowledge has been gained on the transcription network controlled by ERα, however, the mechanism underlying ESR1 (encoding ERα) expression is less understood. We recently discovered that the Hippo pathway is required for the proper expression of ESR1. YAP/TAZ are transcription coactivators that are phosphorylated and inhibited by the Hippo pathway kinase LATS. Here we delineated the molecular mechanisms underlying ESR1 transcription repression by the Hippo pathway. Mechanistically, YAP binds to TEAD to increase local chromatin accessibility to stimulate transcription of nearby genes. Among the YAP target genes, Vestigial-Like Protein 3 (VGLL3) competes with YAP/TAZ for binding to TEAD transcription factor and recruits the NCOR2/SMRT repressor to the super-enhancer of ESR1 gene, leading to epigenetic alteration and transcriptional silencing. We developed a potent LATS inhibitor VT02956. Targeting the Hippo pathway by VT02956 represses ESR1 expression and inhibits the growth of ER

Indexed as

Breast NeoplasmsEstrogen Receptor alphaHippo Signaling PathwayAdaptor Proteins, Signal TransducingFemaleHumansIntracellular Signaling Peptides and ProteinsPhosphoproteinsProtein Serine-Threonine KinasesSignal TransductionTranscription FactorsYAP-Signaling ProteinsAdaptor Proteins, Signal TransducingESR1 protein, humanEstrogen Receptor alphaIntracellular Signaling Peptides and ProteinsPhosphoproteinsProtein Serine-Threonine KinasesTranscription FactorsVGLL3 protein, humanYAP-Signaling Proteins

Identifiers

PMID35217640
PMCPMC8881512
OpenAlexW4214710575

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.