Evidence map›Paper›PMID 34021238›Full record

ArticleCommunications biology2021

Genome-wide CRISPR/Cas9 deletion screen defines mitochondrial gene essentiality and identifies routes for tumour cell viability in hypoxia.

Luke W Thomas, Cinzia Esposito, Rachel E Morgan, Stacey Price, Jamie Young, Steven P Williams, Lucas A Maddalena, Ultan McDermott, Margaret Ashcroft

Open access · goldAbstract read
In one paragraph

Article in Communications biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
3.1field-weighted citation impact, top 7% 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

16 citing papers in PubMed, 30 citations in OpenAlex.

  1. Review
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  13. Editorial: Mitochondria as a hub in cellular signaling.Frontiers in cell and developmental biology · 2022
    Article
  14. HSA-miR-34a-5p regulates the SIRT1/TP53 axis in prostate cancer.American journal of translational research · 2022
    Article
  15. Therapeutic targeting of the hypoxic tumour microenvironment.Nature reviews. Clinical oncology · 2021
    Review
  16. The Contextual Essentiality of Mitochondrial Genes in Cancer.Frontiers in cell and developmental biology · 2021
    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

9 authors at 3 institutions in 2 countries.

Luke W Thomas *Department of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.ORCID 0000-0002-2246-0361
Cinzia Esposito *Department of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
Rachel E MorganDepartment of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
Stacey PriceWellcome Sanger Institute, Hinxton, CB10 1SA, UK.
Jamie YoungWellcome Sanger Institute, Hinxton, CB10 1SA, UK.
Steven P WilliamsWellcome Sanger Institute, Hinxton, CB10 1SA, UK.
Lucas A MaddalenaDepartment of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
Ultan McDermottWellcome Sanger Institute, Hinxton, CB10 1SA, UK.
Margaret AshcroftDepartment of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK. m.ashcroft@medschl.cam.ac.uk.ORCID 0000-0002-0066-3707
University of Cambridge · GBWellcome Sanger Institute · GBUniversity of Zurich · CH

Funding

Cancer Research UK 19442Cancer Research UK C7358/A19442Cancer Research UK RG91141Medical Research Council MR/K002201/2Wellcome Trust 209749/Z/17/ZWellcome Trust RG93172
6 · The paper itself

Abstract

Mitochondria are typically essential for the viability of eukaryotic cells, and utilize oxygen and nutrients (e.g. glucose) to perform key metabolic functions that maintain energetic homeostasis and support proliferation. Here we provide a comprehensive functional annotation of mitochondrial genes that are essential for the viability of a large panel (625) of tumour cell lines. We perform genome-wide CRISPR/Cas9 deletion screening in normoxia-glucose, hypoxia-glucose and normoxia-galactose conditions, and identify both unique and overlapping genes whose loss influences tumour cell viability under these different metabolic conditions. We discover that loss of certain oxidative phosphorylation (OXPHOS) genes (e.g. SDHC) improves tumour cell growth in hypoxia-glucose, but reduces growth in normoxia, indicating a metabolic switch in OXPHOS gene function. Moreover, compared to normoxia-glucose, loss of genes involved in energy-consuming processes that are energetically demanding, such as translation and actin polymerization, improve cell viability under both hypoxia-glucose and normoxia-galactose. Collectively, our study defines mitochondrial gene essentiality in tumour cells, highlighting that essentiality is dependent on the metabolic environment, and identifies routes for regulating tumour cell viability in hypoxia.

Indexed as

Cell ProliferationCRISPR-Cas SystemsGenes, MitochondrialGenome, MitochondrialGlycolysisHumansHypoxiaMitochondriaNeoplasmsOxidative PhosphorylationTumor Cells, Cultured

Identifiers

PMID34021238
PMCPMC8140129
OpenAlexW3163347686

What OpenQuestion holds

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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.