Evidence map›Paper›PMID 30206654›Full record

ArticleDer Pathologe2018

[YAP induces chromosomal instability in liver cancer patients].

S Weiler

Abstract read
PubMed Publisher
In one paragraph

Article in Der Pathologe, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.4field-weighted citation impact, top 42% of its field
1 · What the graph read from it

What it found

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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

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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

1 citing paper in PubMed, 4 citations in OpenAlex.

  1. 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

1 author at 1 institution in 1 country.

S WeilerPathologisches Institut, Universität Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Deutschland. sofia.weiler@med.uni-heidelberg.de.
Heidelberg University · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe Hippo/YAP signaling pathway is a central regulator of organ growth and cell proliferation. Activation of the transcriptional co-activator and oncogene YAP (yes-associated protein) supports the development of liver cancer.

aimsThe aim of this work was to analyze the molecular mechanisms which are responsible for YAP-induced hepatocarcinogenesis.

methodsYAP was silenced using siRNAs in liver cancer cell lines and effects on target gene expression were analyzed via real-time polymerase chain reaction (PCR) and western immunoblotting. Immunoprecipitation and chromatin immunoprecipitation was used to study interacting proteins and binding to target gene promoter regions, respectively. Transgenic mice with liver-specific and inducible YAP expression were used for in vivo analysis. Gene expression data from hepatocellular carcinoma (HCC) patients were used to analyze YAP-dependent gene signatures and to correlate with clinical data. HCC tissue microarrays were analyzed using immunohistochemistry.

resultsTogether with the transcription factors TEAD4 and FOXM1, YAP induces the expression of genes which are responsible for the development of chromosomal instability (CIN). The overexpression of these CIN genes characterizes liver cancer patients with a poor prognosis. Mechanistically, YAP/TEAD4 and FOXM1 bind to the promoter regions of the CIN genes to directly regulate their expression. The treatment of YAP-transgenic mice with a specific FOXM1 inhibitor reduces the YAP-dependent hepatomegaly, CIN gene expression and CIN. The analysis of human HCC tissue samples confirms the statistical correlation between YAP, FOXM1 and CIN. DISCUSSION: These results reveal a new oncogenic mechanism of the Hippo/YAP signaling pathway and identify YAP and FOXM1 as potential targets for targeted therapies.

Indexed as

Adaptor Proteins, Signal TransducingCarcinoma, HepatocellularForkhead Box Protein M1Liver NeoplasmsAdultAnimalsCell Cycle ProteinsCell Line, TumorCell ProliferationChromosomal InstabilityDNA-Binding ProteinsGene Expression Regulation, NeoplasticHumansMiceMuscle ProteinsPhosphoproteinsAdaptor Proteins, Signal TransducingCell Cycle ProteinsDNA-Binding ProteinsForkhead Box Protein M1FOXM1 protein, humanMuscle ProteinsPhosphoproteinsTEAD4 protein, humanTEA Domain Transcription FactorsTranscription FactorsYap1 protein, mouseYAP-Signaling ProteinsCell proliferationChromosomal instabilityGene signatureHepatocellular carcinomaTranscription factors

Identifiers

PMID30206654
OpenAlexW2890024907

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Registered trials

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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.