Evidence map›Paper›PMID 41820368›Full record

ArticleNature communications2026

VHL synthetic lethality screens uncover CBF-β as a negative regulator of STING.

James A C Bertlin, Tekle Pauzaite, Qian Liang, Niek Wit, James C Williamson, Jia Jhing Sia, Nicholas J Matheson, Brian M Ortmann, Thomas J Mitchell, Anneliese O Speak and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

James A C BertlinCambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Jeffrey Cheah Biomedical Centre, Department of Medicine, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0009-0001-9384-5883
Tekle PauzaiteCambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Jeffrey Cheah Biomedical Centre, Department of Medicine, University of Cambridge, Cambridge, UK.
Qian LiangSimmons Comprehensive Cancer Center, Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Niek WitCambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Jeffrey Cheah Biomedical Centre, Department of Medicine, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0009-0002-4330-5333
James C WilliamsonCambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Jeffrey Cheah Biomedical Centre, Department of Medicine, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0002-2009-189X
Jia Jhing SiaCambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Jeffrey Cheah Biomedical Centre, Department of Medicine, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0003-4750-3417
Nicholas J MathesonCambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Jeffrey Cheah Biomedical Centre, Department of Medicine, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0002-3318-1851
Brian M OrtmannCambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Jeffrey Cheah Biomedical Centre, Department of Medicine, University of Cambridge, Cambridge, UK.
Thomas J MitchellEarly Cancer Institute and Department of Surgery, University of Cambridge, Cambridge, UK.
Anneliese O SpeakCambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Jeffrey Cheah Biomedical Centre, Department of Medicine, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0003-4890-4685
Qing ZhangSimmons Comprehensive Cancer Center, Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0002-6595-8995
James A NathanCambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Jeffrey Cheah Biomedical Centre, Department of Medicine, University of Cambridge, Cambridge, UK. jan33@cam.ac.uk.ORCID http://orcid.org/0000-0002-0248-1632

Funding

Identification of DCLK2-TBK1 signaling axis as a potential therapeutic target in kidney cancerR01CA284591 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI Qing Zhang · 2023 to 2026
$1.9M
NCI NIH HHS R01 CA284591Wellcome Trust
6 · The paper itself

Abstract

Clear cell renal cell carcinoma (ccRCC) represents the most common form of kidney cancer and is typified by biallelic inactivation of the von Hippel-Lindau (VHL) tumour suppressor gene. Here, we undertake genome-wide CRISPR/Cas9 screening to reveal synthetic lethal interactors of VHL, and uncover that loss of Core Binding Factor β (CBF-β) causes cell death in VHL-null ccRCC cell lines and impairs tumour establishment and growth in vivo. This synthetic relationship is independent of the elevated activity of hypoxia inducible factors (HIFs) in VHL-null cells, but does involve the RUNX transcription factors that are known binding partners of CBF-β. Mechanistically, CBF-β loss leads to upregulation of type I interferon signalling, and we uncover a direct inhibitory role for CBF-β at the STING locus controlling Interferon Stimulated Gene expression. Targeting CBF-β in kidney cancer both selectively induces tumour cell lethality and promotes activation of type I interferon signalling.

Indexed as

Carcinoma, Renal CellCore Binding Factor beta SubunitKidney NeoplasmsMembrane ProteinsSynthetic Lethal MutationsVon Hippel-Lindau Tumor Suppressor ProteinAnimalsCell Line, TumorcGAS-STING Signaling PathwayCRISPR-Cas SystemsGene Expression Regulation, NeoplasticHumansInterferon Type IMiceSignal TransductionSTING ProteinCore Binding Factor beta SubunitInterferon Type IMembrane ProteinsSTING1 protein, humanSTING ProteinVHL protein, humanVon Hippel-Lindau Tumor Suppressor Protein

Identifiers

PMID41820368
PMCPMC13121600

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.