Evidence map›Paper›PMID 39126118›Full record

ArticleInternational journal of molecular sciences2024

CRKL Enhances YAP Signaling through Binding and JNK/JUN Pathway Activation in Liver Cancer.

Marie C Wesener, Sofia M E Weiler, Michaela Bissinger, Tobias F Klessinger, Fabian Rose, Sabine Merker, Marcin Luzarowski, Thomas Ruppert, Barbara Helm, Ursula Klingmüller and 2 more

Abstract read
In one paragraph

Article in International journal of molecular sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
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

9 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Poor efficacy of anti PD-1 antibody based immunotherapy in patients with acral melanoma: results from the Spanish Melanoma Group (GEM) registry.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Article
  5. Expression and prognostic significance of CRKL in clear cell renal cell carcinoma.American journal of clinical and experimental immunology · 2026
    Article
  6. Article
  7. The intersection ofFrontiers in cellular and infection microbiology · 2025
    Review
  8. Review
  9. 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

12 authors.

Marie C WesenerInstitute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, Germany.
Sofia M E WeilerInstitute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, Germany.
Michaela BissingerInstitute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, Germany.
Tobias F KlessingerInstitute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, Germany.
Fabian RoseInstitute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, Germany.
Sabine MerkerCFMP, Core Facility for Mass Spectrometry & Proteomics at the Center for Molecular Biology (ZMBH), Heidelberg University, 69120 Heidelberg, Germany.ORCID 0009-0000-4052-9927
Marcin LuzarowskiCFMP, Core Facility for Mass Spectrometry & Proteomics at the Center for Molecular Biology (ZMBH), Heidelberg University, 69120 Heidelberg, Germany.
Thomas RuppertCFMP, Core Facility for Mass Spectrometry & Proteomics at the Center for Molecular Biology (ZMBH), Heidelberg University, 69120 Heidelberg, Germany.
Barbara HelmDKFZ, German Cancer Research Center Heidelberg, 69120 Heidelberg, Germany.
Ursula KlingmüllerDKFZ, German Cancer Research Center Heidelberg, 69120 Heidelberg, Germany.
Peter SchirmacherInstitute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, Germany.
Kai BreuhahnInstitute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, Germany.

Funding

Deutsche Forschungsgemeinschaft SFB/TR 209 "Liver Cancer" 314905040
6 · The paper itself

Abstract

The Hippo pathway transducers yes-associated protein (YAP) and WW-domain containing transcription regulator 1 (WWTR1/TAZ) are key regulators of liver tumorigenesis, promoting tumor formation and progression. Although the first inhibitors are in clinical trials, targeting the relevant upstream regulators of YAP/TAZ activity could prove equally beneficial. To identify regulators of YAP/TAZ activity in hepatocarcinoma (HCC) cells, we carried out a proximity labelling approach (BioID) coupled with mass spectrometry. We verified CRK-like proto-oncogene adaptor protein (CRKL) as a new YAP-exclusive interaction partner. CRKL is highly expressed in HCC patients, and its expression is associated with YAP activity as well as poor survival prognosis. In vitro experiments demonstrated CRKL-dependent cell survival and the loss of YAP binding induced through actin disruption. Moreover, we delineated the activation of the JNK/JUN pathway by CRKL, which promoted YAP transcription. Our data illustrate that CRKL not only promoted YAP activity through its binding but also through the induction of YAP transcription by JNK/JUN activation. This emphasizes the potential use of targeting the JNK/JUN pathway to suppress YAP expression in HCC patients.

Indexed as

Adaptor Proteins, Signal TransducingCarcinoma, HepatocellularLiver NeoplasmsNuclear ProteinsTranscription FactorsYAP-Signaling ProteinsCell Line, TumorGene Expression Regulation, NeoplasticHumansMAP Kinase Signaling SystemProtein BindingProto-Oncogene MasSignal TransductionAdaptor Proteins, Signal TransducingCRKL proteinMAS1 protein, humanNuclear ProteinsProto-Oncogene MasTranscription FactorsYAP1 protein, humanYAP-Signaling ProteinsAP1BioIDc-JunCRKHCCHippoMSproteomicssurvivalTEAD

Identifiers

PMID39126118
PMCPMC11312940

What OpenQuestion holds

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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.