Evidence map›Paper›PMID 34859607›Full record

ArticleJournal of extracellular vesicles2021

Secretion of pro-angiogenic extracellular vesicles during hypoxia is dependent on the autophagy-related protein GABARAPL1.

Tom G Keulers, Sten F Libregts, Joel E J Beaumont, Kim G Savelkouls, Johan Bussink, Hans Duimel, Ludwig Dubois, Marijke I Zonneveld, Carmen López-Iglesias, Karel Bezstarosti and 4 more

Open access · goldAbstract read
In one paragraph

Article in Journal of extracellular vesicles, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
1.8field-weighted citation impact, top 14% 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

25 citing papers in PubMed, 33 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Review
  16. Review
  17. Review
  18. Review
  19. Autophagy and autophagy-related pathways in cancer.Nature reviews. Molecular cell biology · 2023
    Review
  20. 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

14 authors at 5 institutions in 1 country.

Tom G KeulersDepartment of Radiation Oncology Radiation Oncology (Maastro) / GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre +, Maastricht, Netherlands.
Sten F LibregtsDepartment of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands.
Joel E J BeaumontDepartment of Radiation Oncology Radiation Oncology (Maastro) / GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre +, Maastricht, Netherlands.
Kim G SavelkoulsDepartment of Radiation Oncology Radiation Oncology (Maastro) / GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre +, Maastricht, Netherlands.
Johan BussinkDepartment of Radiation Oncology, Radboud University Medical Center, Nijmegen, Netherlands.
Hans DuimelMicroscopy CORE Lab, Maastricht Multimodal Molecular Imaging Institute, FHML Division of Nanoscopy, University of Maastricht, Maastricht, Netherlands.
Ludwig DuboisThe M-Lab, Department of Precision Medicine, GROW - School of Oncology, Maastricht University, Maastricht, Netherlands.
Marijke I ZonneveldDepartment of Radiation Oncology Radiation Oncology (Maastro) / GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre +, Maastricht, Netherlands.
Carmen López-IglesiasMicroscopy CORE Lab, Maastricht Multimodal Molecular Imaging Institute, FHML Division of Nanoscopy, University of Maastricht, Maastricht, Netherlands.
Karel BezstarostiProteomics Center, Erasmus University Medical Center, Rotterdam, Netherlands.
Jeroen A DemmersProteomics Center, Erasmus University Medical Center, Rotterdam, Netherlands.
Marc VooijsDepartment of Radiation Oncology Radiation Oncology (Maastro) / GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre +, Maastricht, Netherlands.
Marca WaubenDepartment of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands.
Kasper M A RouschopDepartment of Radiation Oncology Radiation Oncology (Maastro) / GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre +, Maastricht, Netherlands.ORCID 0000-0002-4208-5415
Maastricht University Medical Centre · NLErasmus MC · NLMaastricht University · NLUniversity of Applied Sciences Utrecht · NLRadboud University Nijmegen · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Tumour hypoxia is a hallmark of solid tumours and contributes to tumour progression, metastasis development and therapy resistance. In response to hypoxia, tumour cells secrete pro-angiogenic factors to induce blood vessel formation and restore oxygen supply to hypoxic regions. Extracellular vesicles (EVs) are emerging as mediators of intercellular communication in the tumour microenvironment. Here we demonstrate that increased expression of the LC3/GABARAP protein family member GABARAPL1, is required for endosomal maturation, sorting of cargo to endosomes and the secretion of EVs. Silencing GABARAPL1 results in a block in the early endosomal pathway and impaired secretion of EVs with pro-angiogenic properties. Tumour xenografts of doxycycline inducible GABARAPL1 knockdown cells display impaired vascularisation that results in decreased tumour growth, elevated tumour necrosis and increased therapy efficacy. Moreover, our data show that GABARAPL1 is expressed on the EV surface and targeting GABARAPL1

Indexed as

Adaptor Proteins, Signal TransducingAutophagy-Related ProteinsCell HypoxiaExtracellular VesiclesHumansMicrotubule-Associated ProteinsAdaptor Proteins, Signal TransducingAutophagy-Related ProteinsGABARAPL1 protein, humanMicrotubule-Associated Proteinsautophagyexosomesextracellular vesiclesGABARAPL1hypoxia

Identifiers

PMID34859607
PMCPMC8640512
OpenAlexW3215622442

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.