Evidence map›Paper›PMID 30158528›Full record

ArticleNature communications2018

A feed forward loop enforces YAP/TAZ signaling during tumorigenesis.

Mandeep K Gill, Tania Christova, Ying Y Zhang, Alex Gregorieff, Liang Zhang, Masahiro Narimatsu, Siyuan Song, Shawn Xiong, Amber L Couzens, Jiefei Tong and 8 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 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
4.4field-weighted citation impact, top 5% 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

57 citing papers in PubMed, 97 citations in OpenAlex.

  1. Article
  2. Article
  3. Targeting the Hippo pathway in cancer.Nature reviews. Drug discovery · 2025
    Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. The multifaceted roles of the transcriptional coactivator TAZ in extravillous trophoblast development of the human placenta.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  11. Review
  12. Review
  13. Article
  14. NUAK: never underestimate a kinase.Essays in biochemistry · 2024
    Review
  15. Review
  16. Article
  17. Review
  18. Article
  19. Review
  20. Article
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

18 authors at 4 institutions in 3 countries.

Mandeep K GillDepartment of Biochemistry, University of Toronto, Toronto, ON, M5S 1A8, Canada.ORCID http://orcid.org/0000-0002-0468-9816
Tania ChristovaDepartment of Biochemistry, University of Toronto, Toronto, ON, M5S 1A8, Canada.
Ying Y ZhangDepartment of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A8, Canada.ORCID http://orcid.org/0000-0002-6179-1315
Alex GregorieffCentre for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, M5G 1X5, Canada.
Liang ZhangCentre for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, M5G 1X5, Canada.
Masahiro NarimatsuCentre for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, M5G 1X5, Canada.
Siyuan SongDepartment of Biochemistry, University of Toronto, Toronto, ON, M5S 1A8, Canada.
Shawn XiongDepartment of Biochemistry, University of Toronto, Toronto, ON, M5S 1A8, Canada.
Amber L CouzensCentre for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, M5G 1X5, Canada.
Jiefei TongProgram in Cell Biology, Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada.
Jonathan R KriegerSPARC BioCentre, Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada.
Michael F MoranDepartment of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A8, Canada.
Alexandre R ZlottaDepartment of Surgery, Division of Urology, University of Toronto, Mount Sinai Hospital and University Health Network, Toronto, M5G 1X5, ON, Canada.
Theodorus H van der KwastDepartment of Pathology, Toronto General Hospital, University Health Network, Toronto, ON, M5G 2C4, Canada.
Anne-Claude GingrasDepartment of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A8, Canada.
Frank SicheriDepartment of Biochemistry, University of Toronto, Toronto, ON, M5S 1A8, Canada.
Jeffrey L WranaDepartment of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A8, Canada.
Liliana AttisanoDepartment of Biochemistry, University of Toronto, Toronto, ON, M5S 1A8, Canada. liliana.attisano@utoronto.ca.ORCID http://orcid.org/0000-0003-4824-2642
Mount Sinai Hospital · CAUniversity of Toronto · CAHospital for Sick Children · CAUniversity Health Network · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In most solid tumors, the Hippo pathway is inactivated through poorly understood mechanisms that result in the activation of the transcriptional regulators, YAP and TAZ. Here, we identify NUAK2 as a YAP/TAZ activator that directly inhibits LATS-mediated phosphorylation of YAP/TAZ and show that NUAK2 induction by YAP/TAZ and AP-1 is required for robust YAP/TAZ signaling. Pharmacological inhibition or loss of NUAK2 reduces the growth of cultured cancer cells and mammary tumors in mice. Moreover, in human patient samples, we show that NUAK2 expression is elevated in aggressive, high-grade bladder cancer and strongly correlates with a YAP/TAZ gene signature. These findings identify a positive feed forward loop in the Hippo pathway that establishes a key role for NUAK2 in enforcing the tumor-promoting activities of YAP/TAZ. Our results thus introduce a new opportunity for cancer therapeutics by delineating NUAK2 as a potential target for re-engaging the Hippo pathway.

Indexed as

AcyltransferasesAdaptor Proteins, Signal TransducingCarcinogenesisCell Line, TumorCell Transformation, NeoplasticFemaleHEK293 CellsHumansImmunoblottingImmunoprecipitationMicroscopy, FluorescencePhosphoproteinsPhosphorylationProtein Serine-Threonine KinasesReal-Time Polymerase Chain ReactionSignal TransductionAcyltransferasesAdaptor Proteins, Signal TransducingLATS1 protein, humanLATS2 protein, humanNUAK2 protein, humanPhosphoproteinsProtein Serine-Threonine KinasesTAFAZZIN protein, humanTranscription Factor AP-1Transcription FactorsTumor Suppressor ProteinsYAP1 protein, humanYAP-Signaling Proteins

Identifiers

PMID30158528
PMCPMC6115388
OpenAlexW2888407975

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.