Evidence map›Paper›PMID 27909058›Full record

ArticleThe Journal of biological chemistry2017

Secreted Glioblastoma Nanovesicles Contain Intracellular Signaling Proteins and Active Ras Incorporated in a Farnesylation-dependent Manner.

Natalie Luhtala, Aaron Aslanian, John R Yates, Tony Hunter

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

33 citing papers in PubMed, 50 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
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  5. Review
  6. Article
  7. Review
  8. Exosomes as Novel Diagnostic Biomarkers and Therapeutic Tools in Gliomas.International journal of molecular sciences · 2023
    Review
  9. Article
  10. Article
  11. Article
  12. Pathogenic Extracellular Vesicle (EV) Signaling in Amyotrophic Lateral Sclerosis (ALS).Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022
    Review
  13. Review
  14. Review
  15. Article
  16. Review
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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

4 authors at 2 institutions in 1 country.

Natalie LuhtalaFrom the Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037 and.
Aaron AslanianFrom the Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037 and.
John R Yatesthe Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California 92037.
Tony HunterFrom the Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037 and hunter@salk.edu.
Salk Institute for Biological Studies · USScripps Research Institute · US

Funding

Viral Vector Core (VVC)P30CA014195 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI Ye Zheng · 1985 to 2026
$82.8M
ZDS2P REGULATES SWE1P-DEPENDENT POLARIZED CELL GROWTH IN S CEREVISIAEP41RR011823 · NCRR · UNIVERSITY OF WASHINGTON · PI DAVIS, TRACY · 1996 to 2011
$24.7M
TrainingP41GM103533 · NIGMS · UNIVERSITY OF WASHINGTON · PI MACCOSS, MICHAEL · 2012 to 2021
$20.7M
SOMATIC CELL CYCLE REGULATION BY PHOSPHORYLATIONR01CA080100 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI HUNTER, TONY R. · 1999 to 2018
$13.1M
SIGNAL TRANSDUCTION BY TYROSINE PHOSPHORYLATIONR01CA082683 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI HUNTER, TONY R. · 1999 to 2019
$12.2M
The Invisible Phosphoproteome: New Tools to Study Histidine PhosphorylationR01CA194584 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI HUNTER, TONY R. · 2015 to 2019
$2.2M
NCI NIH HHS P30 CA014195NCI NIH HHS R01 CA080100NCI NIH HHS R01 CA082683NCI NIH HHS R01 CA194584NCRR NIH HHS P41 RR011823NIGMS NIH HHS P41 GM103533
6 · The paper itself

Abstract

Glioblastomas (GBMs) are malignant brain tumors with a median survival of less than 18 months. Redundancy of signaling pathways represented within GBMs contributes to their therapeutic resistance. Exosomes are extracellular nanovesicles released from cells and present in human biofluids that represent a possible biomarker of tumor signaling state that could aid in personalized treatment. Herein, we demonstrate that mouse GBM cell-derived extracellular nanovesicles resembling exosomes from an H-RasV12 myr-Akt mouse model for GBM are enriched for intracellular signaling cascade proteins (GO: 0007242) and Ras protein signal transduction (GO: 0007265), and contain active Ras. Active Ras isolated from human and mouse GBM extracellular nanovesicles lysates using the Ras-binding domain of Raf also coprecipitates with ESCRT (endosomal sorting complex required for transport)-associated exosome proteins Vps4a and Alix. Although we initially hypothesized a role for active Ras protein signaling in exosome biogenesis, we found that GTP binding of K-Ras was dispensable for its packaging within extracellular nanovesicles and for the release of Alix. By contrast, farnesylation of K-Ras was required for its packaging within extracellular nanovesicles, yet expressing a K-Ras farnesylation mutant did not decrease the number of nanovesicles or the amount of Alix protein released per cell. Overall, these results emphasize the primary importance of membrane association in packaging of extracellular nanovesicle factors and indicate that screening nanovesicles within human fluids could provide insight into tissue origin and the wiring of signaling proteins at membranes to predict onset and behavior of cancer and other diseases linked to deregulated membrane signaling states.

Indexed as

PrenylationAnimalsBrain NeoplasmsCalcium-Binding ProteinsCell Cycle ProteinsCell-Derived MicroparticlesCell Line, TumorEndosomal Sorting Complexes Required for TransportGlioblastomaHumansMiceProto-Oncogene Proteins p21(ras)raf KinasesCalcium-Binding ProteinsCell Cycle ProteinsEndosomal Sorting Complexes Required for TransportHras protein, mouseKRAS protein, humanPDCD6IP protein, humanPdcd6ip protein, mouseProto-Oncogene Proteins p21(ras)raf Kinasescell signalingendosomal sorting complexes required for transport (ESCRT)exosome (vesicle)glioblastomaproteomicsRas protein

Identifiers

PMID27909058
PMCPMC5241736
OpenAlexW2558791186

What OpenQuestion holds

Textmetadata
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.