Evidence map›Paper›PMID 35302851›Full record

ArticleScience advances2022

ARAF suppresses ERBB3 expression and metastasis in a subset of lung cancers.

Juliane Mooz, Kristina Riegel, Hari Ps, Anguraj Sadanandam, Federico Marini, Matthias Klein, Ulrike Werner, Wilfried Roth, Annett Wilken-Schmitz, Irmgard Tegeder and 1 more

Open access · goldAbstract read
In one paragraph

Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.0field-weighted citation impact, top 28% 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

17 citing papers in PubMed, 13 citations in OpenAlex.

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  10. Clear cell renal carcinoma essentially requires CDKL3 for oncogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2025
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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

11 authors at 3 institutions in 2 countries.

Juliane MoozCell Biology Unit, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany.ORCID 0000-0002-0877-847X
Kristina RiegelCell Biology Unit, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany.ORCID 0000-0002-3656-8453
Hari PsDivision of Molecular Pathology, The Institute of Cancer Research, London, UK.ORCID 0000-0003-3580-962X
Anguraj SadanandamDivision of Molecular Pathology, The Institute of Cancer Research, London, UK.ORCID 0000-0001-8485-5150
Federico MariniInstitute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany.ORCID 0000-0003-3252-7758
Matthias KleinInstitute of Immunology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany.
Ulrike WernerIndivumed GmbH, Hamburg, Germany.
Wilfried RothInstitute of Pathology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany.
Annett Wilken-SchmitzInstitute of Clinical Pharmacology, Goethe-University, Medical Faculty, Frankfurt (Main), Germany.
Irmgard TegederInstitute of Clinical Pharmacology, Goethe-University, Medical Faculty, Frankfurt (Main), Germany.ORCID 0000-0001-7524-8025
Krishnaraj RajalingamCell Biology Unit, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany.ORCID 0000-0002-4175-9633
Johannes Gutenberg University Mainz · DEGoethe University Frankfurt · DEInstitute of Cancer Research · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

RAF kinases are highly conserved serine/threonine kinases, and among the three RAF isoforms (ARAF, BRAF, and CRAF), the pathophysiological relevance of ARAF is not well defined. Here, we show that patients with lung cancer exhibit low expression of ARAF, which is associated with lymph node metastasis and poor patient survival. We uncover that depletion of ARAF promotes anchorage-independent growth and metastasis through activation of AKT signaling in a subset of lung cancer cells. We identified that loss of ARAF was associated with an increase in ERBB3 expression in a kinase-independent manner. ARAF suppressed the promoter activity of ERBB3, and reconstitution of ARAF in ARAF-depleted cells led to the reversal of enhanced ERBB3-AKT signaling. Furthermore, ARAF inhibited neuregulin 1 (hNRG1)-mediated AKT activation through controlling ERBB3 expression via the transcription factor KLF5. Our results disclose a critical dual role for ARAF kinase in the negative regulation of ERBB3-AKT signaling, thereby suppressing tumor metastasis.

Indexed as

Lung Neoplasmsraf KinasesHumansProtein Serine-Threonine KinasesReceptor, ErbB-3Signal TransductionERBB3 protein, humanProtein Serine-Threonine Kinasesraf KinasesReceptor, ErbB-3

Identifiers

PMID35302851
PMCPMC8932670
OpenAlexW4220800523

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.