Evidence map›Paper›PMID 23563179›Full record

ArticleOncogene2014

An evolutionary shift in the regulation of the Hippo pathway between mice and flies.

W Bossuyt, C-L Chen, Q Chen, M Sudol, H McNeill, D Pan, A Kopp, G Halder

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

Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.

0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed
9.9field-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

80 citing papers in PubMed, 110 citations in OpenAlex.

  1. Article
  2. Article
  3. Targeting the Hippo pathway in cancer.Nature reviews. Drug discovery · 2025
    Review
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20 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

8 authors at 6 institutions in 3 countries.

W Bossuyt1] Vlaams Instituut voor Biotechnologie (VIB) Center for the Biology of Disease, Leuven, Belgium [2] Kuleuven, Center for Human Genetics, Leuven, Belgium [3] The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
C-L ChenThe University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
Q ChenDepartment of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
M SudolWeis Center for Research, Laboratory of Signal Transduction, Geisinger Clinic, Danville, PA, USA.
H McNeillSamuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
D PanDepartment of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
A KoppDepartment of Evolution and Ecology, University of California-Davis, Davis, CA, USA.
G Halder1] Vlaams Instituut voor Biotechnologie (VIB) Center for the Biology of Disease, Leuven, Belgium [2] Kuleuven, Center for Human Genetics, Leuven, Belgium [3] The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
Johns Hopkins University · USThe University of Texas MD Anderson Cancer Center · USGeisinger Medical Center · USLunenfeld-Tanenbaum Research Institute · CAUniversity of California, Davis · USVlaams Instituut voor Biotechnologie · BE

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI Rosalie Wollett · 1985 to 2026
$208.6M
Regulation of organ size in vivoR01GM067997 · NIGMS · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI HALDER, GEORG A · 2003 to 2011
$2.7M
Howard Hughes Medical InstituteNCI NIH HHS P30 CA006973NIGMS NIH HHS GM067997NIGMS NIH HHS R01 GM067997
6 · The paper itself

Abstract

The Hippo pathway plays a key role in controlling organ growth in many animal species and its deregulation is associated with different types of cancer. Understanding the regulation of the Hippo pathway and discovering upstream regulators is thus a major quest. Interestingly, while the core of the Hippo pathway contains a highly conserved kinase cascade, different components have been identified as upstream regulators in Drosophila and vertebrates. However, whether the regulation of the Hippo pathway is indeed different between Drosophila and vertebrates or whether these differences are due to our limited analysis of these components in different organisms is not known. Here we show that the mouse Fat4 cadherin, the ortholog of the Hippo pathway regulator Fat in Drosophila, does not apparently regulate the Hippo pathway in the murine liver. In fact, we uncovered an evolutionary shift in many of the known upstream regulators at the base of the arthropod lineage. In this evolutionary transition, Fat and the adaptor protein Expanded gained novel domains that connected them to the Hippo pathway, whereas the cell-adhesion receptor Echinoid evolved as a new protein. Subsequently, the junctional adaptor protein Angiomotin (Amot) was lost and the downstream effector Yap lost its PDZ-binding motif that interacts with cell junction proteins. We conclude that fundamental differences exist in the upstream regulatory mechanisms of Hippo signaling between Drosophila and vertebrates.

Indexed as

Signal TransductionAnimalsCadherinsCell Adhesion MoleculesCell PolarityDrosophila melanogasterDrosophila ProteinsEvolution, MolecularFeedback, PhysiologicalGenes, Tumor SuppressorHippo KinasesHippo Signaling PathwayIntracellular Signaling Peptides and ProteinsLarvaLiverMaleCadherinsCell Adhesion MoleculesDrosophila ProteinsED protein, DrosophilaFat4 protein, mouseHippo Kinaseshpo protein, DrosophilaIntracellular Signaling Peptides and ProteinsNuclear ProteinsProtein Serine-Threonine KinasesRepressor ProteinsTrans-ActivatorsYAP-Signaling ProteinsYki protein, Drosophila

Identifiers

PMID23563179
PMCPMC4613760
OpenAlexW1978947310

What OpenQuestion holds

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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.