Evidence map›Paper›PMID 30478285›Full record

ArticleScientific reports2018

Usp9X Regulates Cell Death in Malignant Peripheral Nerve Sheath Tumors.

E Bianchetti, S J Bates, S L Carroll, M D Siegelin, K A Roth

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

10 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
  2. Article
  3. Mechanisms of MCL-1 Protein Stability Induced by MCL-1 Antagonists in B-Cell Malignancies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023
    Article
  4. Methodological Approaches for Assessing Metabolomic Changes in Glioblastomas.Methods in molecular biology (Clifton, N.J.) · 2022
    Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. 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

5 authors at 2 institutions in 1 country.

E BianchettiDepartment of Pathology & Cell Biology, Columbia University Vagelos College of Physicians and Surgeons, New York, USA. eb2985@cumc.columbia.edu.
S J BatesDepartment of Pathology & Cell Biology, Columbia University Vagelos College of Physicians and Surgeons, New York, USA.
S L CarrollMedical University of South Carolina, Department of Pathology and Laboratory Medicine, Charleston, South Carolina, USA.
M D SiegelinDepartment of Pathology & Cell Biology, Columbia University Vagelos College of Physicians and Surgeons, New York, USA.
K A RothDepartment of Pathology & Cell Biology, Columbia University Vagelos College of Physicians and Surgeons, New York, USA.ORCID http://orcid.org/0000-0002-0643-995X
Columbia University · USMedical University of South Carolina · US

Funding

Tumor Biology and Microenvironment ProgramP30CA013696 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI Anil K Rustgi · 1985 to 2026
$115.3M
South Carolina Cancer Disparities Research Center (SC CADRE)U54CA210962 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI TURNER, DAVID PAUL · 2017 to 2023
$6.7M
South Carolina Cancer Disparities Research Center (SC CaDRe)U54CA210963 · NCI · SOUTH CAROLINA STATE UNIVERSITY · PI FORD, MARVELLA ELIZABETH, SALLEY, JUDITH · 2017 to 2023
$6.1M
Targeting Mutant IDH1 for a Novel Synthetic Lethal Interaction in Malignant GliomasR01NS102366 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SIEGELIN, MARKUS D · 2018 to 2022
$1.8M
Dual Inhibition of Mitochondrial Matrix Chaperones and Anti-Apoptotic Bcl-2 Family Members for Glioblastoma Therapy.R01NS095848 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SIEGELIN, MARKUS D · 2016 to 2020
$1.8M
Overcoming apoptotic resistance in glioblastoma by CP-d/n-ATF5, a novel tumor speK08NS083732 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SIEGELIN, MARKUS D · 2014 to 2018
$938k
Becton Dickinson LSR II Analytical Flow CytometerS10RR027050 · NCRR · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CLYNES, RAPHAEL A. · 2011 to 2011
$413k
NCI NIH HHS P30 CA013696NCI NIH HHS U54 CA210962NCI NIH HHS U54 CA210963NCRR NIH HHS S10 RR027050NINDS NIH HHS K08 NS083732NINDS NIH HHS R01 NS095848NINDS NIH HHS R01 NS102366U.S. Department of Defense (DOD) W81XWH-12-1-0164U.S. Department of Defense (DOD) W81XWH-14-1-0073U.S. Department of Defense (DOD) X81XWH-15-1-0193
6 · The paper itself

Abstract

Malignant peripheral nerve sheath tumors (MPNSTs) are the leading cause of death in neurofibromatosis type 1 (NF1) patients. Current treatment modalities have been largely unsuccessful in improving MPNST patient survival, making the identification of new therapeutic targets urgent. In this study, we found that interference with Usp9X, a deubiquitinating enzyme which is overexpressed in nervous system tumors, or Mcl-1, an anti-apoptotic member of the Bcl-2 family whose degradation is regulated by Usp9X, causes rapid death in human MPNST cell lines. Although both Usp9X and Mcl-1 knockdown elicited some features of apoptosis, broad spectrum caspase inhibition was ineffective in preventing knockdown-induced MPNST cell death suggesting that caspase-independent death pathways were also activated. Ultrastructural examination of MPNST cells following either Usp9X interference or pharmacological inhibition showed extensive cytoplasmic vacuolization and swelling of endoplasmic reticulum (ER) and mitochondria most consistent with paraptotic cell death. Finally, the Usp9X pharmacological inhibitor WP1130 significantly reduced human MPNST growth and induced tumor cell death in an in vivo xenograft model. In total, these findings indicate that Usp9X and Mcl-1 play significant roles in maintaining human MPNST cell viability and that pharmacological inhibition of Usp9X deubiquitinase activity could be a therapeutic target for MPNST treatment.

Indexed as

AnimalsApoptosisCell DeathCell Line, TumorCell ProliferationCell SurvivalEndoplasmic ReticulumGene Expression Regulation, NeoplasticHumansMiceMice, SCIDMitochondriaNerve Sheath NeoplasmsNeurofibromatosis 1Proto-Oncogene Proteins c-bcl-2Ubiquitin ThiolesteraseProto-Oncogene Proteins c-bcl-2Ubiquitin ThiolesteraseUSP9X protein, human

Identifiers

PMID30478285
PMCPMC6255814
OpenAlexW2901815488

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.