Evidence map›Paper›PMID 29382819›Full record

ArticleNature communications2018

RASSF1A uncouples Wnt from Hippo signalling and promotes YAP mediated differentiation via p73.

Angelos Papaspyropoulos, Leanne Bradley, Asmita Thapa, Chuen Yan Leung, Konstantinos Toskas, Delia Koennig, Dafni-Eleftheria Pefani, Cinzia Raso, Claudia Grou, Garth Hamilton and 14 more

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

Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed
6.9field-weighted citation impact, top 2% 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

58 citing papers in PubMed, 100 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
  5. On the mechanisms of epidermal stemness and differentiation.NPJ systems biology and applications · 2025
    Article
  6. Interrogating the regulatory epigenome of cellular senescence.Cellular and molecular life sciences : CMLS · 2025
    Review
  7. Review
  8. Article
  9. Article
  10. YAP/TAZ Signalling Controls Epidermal Keratinocyte Fate.International journal of molecular sciences · 2024
    Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. A GATA2-CDC6 axis modulates androgen receptor blockade-induced senescence in prostate cancer.Journal of experimental & clinical cancer research : CR · 2023
    Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Review
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

24 authors at 3 institutions in 3 countries.

Angelos PapaspyropoulosCRUK/MRC Oxford Institute, Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK.
Leanne BradleyCRUK/MRC Oxford Institute, Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK.
Asmita ThapaCRUK/MRC Oxford Institute, Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK.
Chuen Yan LeungThe Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, CB2 1QN, UK.
Konstantinos ToskasCRUK/MRC Oxford Institute, Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK.
Delia KoennigCRUK/MRC Oxford Institute, Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK.
Dafni-Eleftheria PefaniCRUK/MRC Oxford Institute, Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK.
Cinzia RasoSystems Biology Ireland, University College Dublin, Dublin 4, Ireland.
Claudia GrouCRUK/MRC Oxford Institute, Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK.
Garth HamiltonCRUK/MRC Oxford Institute, Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK.
Nikola VlahovCRUK/MRC Oxford Institute, Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK.
Anna GrawendaCRUK/MRC Oxford Institute, Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK.
Syed HaiderApplied Computational Genomics, Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK.
Jagat ChauhanApplied Computational Genomics, Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK.
Ludovico ButiLudwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, OX3 7DQ, UK.
Alexander KanapinBioinformatics Research Core, Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK.ORCID http://orcid.org/0000-0001-9802-5297
Xin LuLudwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, OX3 7DQ, UK.
Francesca BuffaApplied Computational Genomics, Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK.ORCID http://orcid.org/0000-0003-0409-406X
Grigory DianovCRUK/MRC Oxford Institute, Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK.
Alex von KriegsheimSystems Biology Ireland, University College Dublin, Dublin 4, Ireland.
David MatallanasSystems Biology Ireland, University College Dublin, Dublin 4, Ireland.
Anastasia SamsonovaBioinformatics Research Core, Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK.
Magdalena Zernicka-GoetzThe Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, CB2 1QN, UK.
Eric O'NeillCRUK/MRC Oxford Institute, Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK. eric.oneill@oncology.ox.ac.uk.ORCID http://orcid.org/0000-0002-0060-6278
University of Oxford · GBUniversity College Dublin · IEUniversity of Cambridge · GB

Funding

Cancer Research UK 19277Cancer Research UK 23969Medical Research Council MC_PC_12002Wellcome Trust
6 · The paper itself

Abstract

Transition from pluripotency to differentiation is a pivotal yet poorly understood developmental step. Here, we show that the tumour suppressor RASSF1A is a key player driving the early specification of cell fate. RASSF1A acts as a natural barrier to stem cell self-renewal and iPS cell generation, by switching YAP from an integral component in the β-catenin-TCF pluripotency network to a key factor that promotes differentiation. We demonstrate that epigenetic regulation of the Rassf1A promoter maintains stemness by allowing a quaternary association of YAP-TEAD and β-catenin-TCF3 complexes on the Oct4 distal enhancer. However, during differentiation, promoter demethylation allows GATA1-mediated RASSF1A expression which prevents YAP from contributing to the TEAD/β-catenin-TCF3 complex. Simultaneously, we find that RASSF1A promotes a YAP-p73 transcriptional programme that enables differentiation. Together, our findings demonstrate that RASSF1A mediates transcription factor selection of YAP in stem cells, thereby acting as a functional "switch" between pluripotency and initiation of differentiation.

Indexed as

Adaptor Proteins, Signal TransducingAnimalsBasic Helix-Loop-Helix Proteinsbeta CateninCell Cycle ProteinsCell DifferentiationDNA-Binding ProteinsEmbryonic Stem CellsFemaleGene Expression Regulation, DevelopmentalHippo Signaling PathwayHumansMaleMice, Inbred C57BLMice, Inbred CBAOctamer Transcription Factor-3Adaptor Proteins, Signal TransducingBasic Helix-Loop-Helix Proteinsbeta CateninCell Cycle ProteinsCTNNB1 protein, mouseDNA-Binding ProteinsOctamer Transcription Factor-3PhosphoproteinsPou5f1 protein, mouseProtein Serine-Threonine KinasesRASSF1 protein, humanRASSF1 protein, mouseTcf3 protein, mouseTead2 protein, mouseTEA Domain Transcription FactorsTranscription FactorsTrp73 protein, mouseTumor Protein p73Tumor Suppressor ProteinsWnt ProteinsYap1 protein, mouseYAP-Signaling Proteins

Identifiers

PMID29382819
PMCPMC5789973
OpenAlexW2787611996

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.