Evidence map›Paper›PMID 32720716›Full record

ArticleThe EMBO journal2020

Glutamine deprivation alters the origin and function of cancer cell exosomes.

Shih-Jung Fan, Benjamin Kroeger, Pauline P Marie, Esther M Bridges, John D Mason, Kristie McCormick, Christos E Zois, Helen Sheldon, Nasullah Khalid Alham, Errin Johnson and 10 more

Open access · hybridAbstract readVideo-Audio Media
PubMed Full text at PMC Publisher
In one paragraph

Article in The EMBO journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.

0numbers the graph read from it
0cells of the map it votes in
87citing papers in PubMed
5.7field-weighted citation impact, top 3% 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

87 citing papers in PubMed, 117 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Review
  12. Review
  13. Review
  14. Review
  15. Article
  16. Review
  17. Review
  18. Article
  19. Review
  20. Article

27 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 2 institutions in 1 country.

Shih-Jung Fan *Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Benjamin Kroeger *Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.ORCID 0000-0003-1479-3841
Pauline P MarieDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Esther M BridgesDepartment of Oncology, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
John D MasonDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Kristie McCormickDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Christos E ZoisDepartment of Oncology, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Helen SheldonDepartment of Oncology, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Nasullah Khalid AlhamInstitute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, UK.
Errin JohnsonSir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Matthew EllisDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Maria Irina StefanaDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Cláudia C MendesDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Stephen Mark WainwrightDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Christopher CunninghamNuffield Department of Surgical Sciences, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Freddie C HamdyNuffield Department of Surgical Sciences, John Radcliffe Hospital, University of Oxford, Oxford, UK.
John F MorrisDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Adrian L HarrisDepartment of Oncology, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Clive WilsonDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.ORCID 0000-0003-0040-0728
Deborah Ci GoberdhanDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.ORCID 0000-0003-0645-6714
University of Oxford · GBJohn Radcliffe Hospital · GB

Funding

Biotechnology and Biological Sciences Research Council BB/K017462/1Biotechnology and Biological Sciences Research Council BB/L007096/1Cancer Research UK 19076Wellcome Trust 091911Wellcome Trust 107457
6 · The paper itself

Abstract

Exosomes are secreted extracellular vesicles carrying diverse molecular cargos, which can modulate recipient cell behaviour. They are thought to derive from intraluminal vesicles formed in late endosomal multivesicular bodies (MVBs). An alternate exosome formation mechanism, which is conserved from fly to human, is described here, with exosomes carrying unique cargos, including the GTPase Rab11, generated in Rab11-positive recycling endosomal MVBs. Release of Rab11-positive exosomes from cancer cells is increased relative to late endosomal exosomes by reducing growth regulatory Akt/mechanistic Target of Rapamycin Complex 1 (mTORC1) signalling or depleting the key metabolic substrate glutamine, which diverts membrane flux through recycling endosomes. Vesicles produced under these conditions promote tumour cell proliferation and turnover and modulate blood vessel networks in xenograft mouse models in vivo. Their growth-promoting activity, which is also observed in vitro, is Rab11a-dependent, involves ERK-MAPK-signalling and is inhibited by antibodies against amphiregulin, an EGFR ligand concentrated on these vesicles. Therefore, glutamine depletion or mTORC1 inhibition stimulates release from Rab11a compartments of exosomes with pro-tumorigenic functions, which we propose promote stress-induced tumour adaptation.

Indexed as

Cell ProliferationExosomesMAP Kinase Signaling SystemNeoplasmsAnimalsDrosophila melanogasterDrosophila ProteinsGlutamineMechanistic Target of Rapamycin Complex 1rab11 GTP-Binding Proteinsrab GTP-Binding ProteinsDrosophila ProteinsGlutamineMechanistic Target of Rapamycin Complex 1rab11 GTP-Binding ProteinsRab11 protein, Drosophilarab GTP-Binding Proteinsexosomeextracellular vesiclemechanistic Target of Rapamycinmultivesicular bodyRab11(a)

Identifiers

PMID32720716
PMCPMC7429491
OpenAlexW3033987764

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.