Evidence map›Paper›PMID 40841511›Full record

ArticleNature communications2025

Genome-wide in vivo CRISPR screens identify GATOR1 complex as a tumor suppressor in Myc-driven lymphoma.

Margaret A Potts, Shinsuke Mizutani, Yexuan Deng, Srimayee Vaidyanathan, Keziah E Ting, Göknur Giner, Shruti Sridhar, Girija Shenoy, Yang Liao, Sarah T Diepstraten and 22 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. 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

32 authors.

Margaret A Potts *The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.ORCID http://orcid.org/0000-0001-9796-9683
Shinsuke Mizutani *The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
Yexuan Deng *The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
Srimayee VaidyanathanPeter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Keziah E TingPeter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Göknur GinerThe Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
Shruti SridharDepartment of Hematology-Oncology, National University Hospital and Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
Girija ShenoyDepartment of Hematology-Oncology, National University Hospital and Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
Yang LiaoOlivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia.
Sarah T DiepstratenThe Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.ORCID http://orcid.org/0000-0002-1946-5161
Andrew J KuehThe Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
Martin PalThe Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.ORCID http://orcid.org/0000-0002-1563-5426
Geraldine HealeyThe Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
Lin TaiThe Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
Zilu WangThe Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
Christina KönigThe Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.ORCID http://orcid.org/0000-0002-6982-9701
Deeksha KaloniThe Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
Lauren WhelanThe Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
Michael J G MilevskiyThe Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
Hannah D CoughlanThe Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.ORCID http://orcid.org/0000-0002-2392-9942
Giovanna PomilioThe Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
Andrew H WeiThe Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
Jane E VisvaderThe Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.ORCID http://orcid.org/0000-0001-9173-6977
Anthony T PapenfussThe Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.ORCID http://orcid.org/0000-0002-1102-8506
Stephen WilcoxThe Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
Anand D JeyasekharanDepartment of Hematology-Oncology, National University Hospital and Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.ORCID http://orcid.org/0000-0001-9816-6137
Wei ShiOlivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia.
Emily J LelliottThe Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.ORCID http://orcid.org/0000-0002-5028-6938
Gemma L KellyThe Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.ORCID http://orcid.org/0000-0002-6533-1201
Kristin K BrownPeter MacCallum Cancer Centre, Melbourne, Victoria, Australia.ORCID http://orcid.org/0000-0002-4991-8870
Andreas StrasserThe Walter and Eliza Hall Institute of Medical Research, Parkville, Australia. strasser@wehi.edu.au.ORCID http://orcid.org/0000-0002-5020-4891
Marco J HeroldThe Walter and Eliza Hall Institute of Medical Research, Parkville, Australia. marco.herold@onjcri.org.au.ORCID http://orcid.org/0000-0001-7539-7581

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Identifying tumor suppressor genes is predicted to inform on the development of novel strategies for cancer therapy. To identify new lymphoma driving processes that cooperate with oncogenic MYC, which is abnormally highly expressed in ~70% of human cancers, we use a genome-wide CRISPR gene knockout screen in Eµ-Myc;Cas9 transgenic hematopoietic stem and progenitor cells in vivo. We discover that loss of any of the GATOR1 complex components - NPRL3, DEPDC5, NPRL2 - significantly accelerates c-MYC-driven lymphoma development in mice. MYC-driven lymphomas lacking GATOR1 display constitutive mTOR pathway activation and are highly sensitive to mTOR inhibitors, both in vitro and in vivo. These findings identify GATOR1 suppression of mTORC1 as a tumor suppressive mechanism in MYC-driven lymphomagenesis and suggest an avenue for therapeutic intervention in GATOR1-deficient lymphomas through mTOR inhibition.

Indexed as

Genes, Tumor SuppressorLymphomaProto-Oncogene Proteins c-mycAnimalsCell Line, TumorClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsGTPase-Activating ProteinsHumansMechanistic Target of Rapamycin Complex 1MiceMice, KnockoutMice, TransgenicSignal TransductionTOR Serine-Threonine KinasesTumor Suppressor ProteinsGTPase-Activating ProteinsMechanistic Target of Rapamycin Complex 1Proto-Oncogene Proteins c-mycTOR Serine-Threonine KinasesTumor Suppressor Proteins

Identifiers

PMID40841511
PMCPMC12370908

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.