Evidence map›Paper›PMID 24469054›Full record

ArticleOncogene2015

ASC deficiency suppresses proliferation and prevents medulloblastoma incidence.

E R W Knight, E Y Patel, C A Flowers, A J Crowther, J P Ting, C R Miller, T R Gershon, M Deshmukh

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.3field-weighted citation impact, top 41% 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

9 citing papers in PubMed, 10 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Dual Role of Inflammasome Adaptor ASC in Cancer.Frontiers in cell and developmental biology · 2020
    Review
  7. Article
  8. Article
  9. 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

8 authors at 1 institution in 1 country.

E R W Knight1] Neurobiology Curriculum, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA [2] Neuroscience Center, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA.
E Y PatelNeuroscience Center, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA.
C A FlowersNeuroscience Center, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA.
A J Crowther1] Neuroscience Center, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA [2] Lineberger Comprehensive Cancer Center, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA.
J P Ting1] Neurobiology Curriculum, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA [2] Lineberger Comprehensive Cancer Center, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA [3] Department of Microbiology and Immunology, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA.
C R Miller1] Neuroscience Center, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA [2] Lineberger Comprehensive Cancer Center, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA [3] Department of Pathology and Laboratory Medicine, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA [4] Department of Neurology, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA.
T R Gershon1] Neurobiology Curriculum, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA [2] Neuroscience Center, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA [3] Lineberger Comprehensive Cancer Center, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA [4] Department of Neurology, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA.
M Deshmukh1] Neurobiology Curriculum, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA [2] Neuroscience Center, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA [3] Lineberger Comprehensive Cancer Center, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA [4] Department of Cell Biology and Physiology, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA.
University of North Carolina at Chapel Hill · US

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
UNC Neuroscience Center Research Cores: MicroscopyP30NS045892 · NINDS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ZYLKA, MARK J. · 2003 to 2022
$11.5M
Mechanisms of Increasing Apoptosis Regulation in Developing and Mature NeuronsR01NS042197 · NINDS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DESHMUKH, MOHANISH P · 2001 to 2011
$3.5M
Cytochrome c Degradation: A Mechanism to Restrict Apoptosis in Postmitotic CellsR01GM078366 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DESHMUKH, MOHANISH P · 2006 to 2013
$2.6M
Aerobic glycolysis regulates apoptosis in neurogenesis and medulloblastomaK08NS077978 · NINDS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI GERSHON, TIMOTHY · 2012 to 2015
$705k
NCI NIH HHS 3P30CA016086NCI NIH HHS P30 CA016086NIGMS NIH HHS GM078366NIGMS NIH HHS R01 GM078366NINDS NIH HHS 1K08NS077978NINDS NIH HHS K08 NS077978NINDS NIH HHS NS042197NINDS NIH HHS P30 NS045892NINDS NIH HHS R01 NS042197
6 · The paper itself

Abstract

Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is silenced by promoter methylation in many types of tumors, yet ASC's role in most cancers remains unknown. Here, we show that ASC is highly expressed in a model of medulloblastoma, the most common malignant pediatric brain cancer; ASC is also expressed in human medulloblastomas. Importantly, while ASC deficiency did not affect normal cerebellar development, ASC knockout mice on the Smoothened (ND2:SmoA1) transgenic model of medulloblastoma exhibited a profound reduction in medulloblastoma incidence and a delayed tumor onset. A similar decrease in tumorigenesis with ASC deficiency was also seen in the hGFAP-Cre:SmoM2 mouse model of medulloblastoma. Interestingly, hyperproliferation of the external granule layer (EGL) was comparable at P20 in both wild-type and ASC-deficient SmoA1 mice. However, while the apoptosis and differentiation markers remained unchanged at this age, proliferation makers were decreased, and the EGL was reduced in thickness and area by P60. This reduction in proliferation with ASC deficiency was also seen in isolated SmoA1 cerebellar granule precursor cells in vitro, indicating that the effect of ASC deletion on proliferation was cell autonomous. Interestingly, ASC-deficient SmoA1 cerebella exhibited disrupted expression of genes in the transforming growth factor-β pathway and increased level of nuclear Smad3. Taken together, these results demonstrate an unexpected role for ASC in Sonic hedgehog-driven medulloblastoma tumorigenesis, thus identifying ASC as a promising novel target for antitumor therapy.

Indexed as

Cell ProliferationAdolescentAdultAnimalsApoptosis Regulatory ProteinsCARD Signaling Adaptor ProteinsCerebellar NeoplasmsChildChild, PreschoolCytoskeletal ProteinsFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansInfantIn Situ HybridizationApoptosis Regulatory ProteinsCARD Signaling Adaptor ProteinsCytoskeletal ProteinsPYCARD protein, humanPycard protein, mouseTransforming Growth Factor beta

Identifiers

PMID24469054
PMCPMC4520702
OpenAlexW2016912029

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.