Evidence map›Paper›PMID 21948232›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2011

Molecular imaging of TGFβ-induced Smad2/3 phosphorylation reveals a role for receptor tyrosine kinases in modulating TGFβ signaling.

Shyam Nyati, Katrina Schinske, Dipankar Ray, Mukesh K Nyati, Mukesh Nyati, Brian Dale Ross, Alnawaz Rehemtulla

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
1.9field-weighted citation impact, top 15% 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, 41 citations in OpenAlex.

  1. Review
  2. Article
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  8. Molecular Imaging with Reporter Genes: Has Its Promise Been Delivered?Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2019
    Review
  9. Adipose-derived stromal cell secretome disrupts autophagy in glioblastoma.Journal of molecular medicine (Berlin, Germany) · 2019
    Article
  10. Article
  11. Dual Reporter Bioluminescence Imaging with NanoLuc and Firefly Luciferase.Methods in molecular biology (Clifton, N.J.) · 2018
    Article
  12. Article
  13. Article
  14. Quantitative and Dynamic Imaging of ATM Kinase Activity.Methods in molecular biology (Clifton, N.J.) · 2017
    Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
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4 · The record

Corrections and comments

  • Erratum issued
    Nyati, Mukesh [corrected to Nyati, Mukesh K]
5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Shyam NyatiCenter for Molecular Imaging, University of Michigan, Ann Arbor, USA.
Katrina Schinske
Dipankar Ray
Mukesh K Nyati
Mukesh Nyati
Brian Dale Ross
Alnawaz Rehemtulla
University of Michigan–Ann Arbor · US

Funding

QUANTITATION OF HUMAN BRAIN TUMOR THERAPY RESPONSE BY MRP01CA085878 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI JOHNSON, TIMOTHY D · 2001 to 2017
$31.9M
Small Animal Imaging CoreP50CA093990 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ROSS, BRIAN D. · 2002 to 2012
$19.0M
Molecular Imaging of Phospho-FADD and its role in resistance to therapyR01CA129623 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI REHEMTULLA, ALNAWAZ · 2007 to 2011
$1.4M
Targeting SMURF2 as a novel therapy for EGFR driven tumorsR01CA160981 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI RAY, DIPANKAR · 2011 to 2015
$1.4M
HTS for FADD kinase inhibitors using molecular imagingR21CA131859 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI REHEMTULLA, ALNAWAZ · 2008 to 2009
$277k
NCI NIH HHS P01 CA085878NCI NIH HHS P01 CA85878NCI NIH HHS P50 CA093990NCI NIH HHS P50CA093990NCI NIH HHS R01 CA129623NCI NIH HHS R01CA129623NCI NIH HHS R01 CA160981NCI NIH HHS R21 CA131859NCI NIH HHS R21CA131859
6 · The paper itself

Abstract

purposeThe dual modality of TGFβ, both as a potent tumor suppressor and a stimulator of tumor progression, invasion, and metastasis, make it a critical target for therapeutic intervention in human cancers. The ability to carry out real-time, noninvasive imaging of TGFβ-activated Smad signaling in live cells and animal models would significantly improve our understanding of the regulation of this unique signaling cascade. To advance these efforts, we developed a highly sensitive molecular imaging tool that repetitively, noninvasively, and dynamically reports on TGFBR1 kinase activity. EXPERIMENTAL

designThe bioluminescent TGFβR1 reporter construct was developed using a split firefly luciferase gene containing a functional sensor of Smad2 phosphorylation, wherein inhibition of TGFβ receptor1 kinase activity leads to an increase in reporter signaling. The reporter was stably transfected into mammalian cells and used to image in vivo and in vitro bioluminescent activity as a surrogate for monitoring TGFBR1 kinase activity.

resultsThe reporter was successfully used to monitor direct and indirect inhibition of TGFβ-induced Smad2 and SMAD3 phosphorylation in live cells and tumor xenografts and adapted for high-throughput screening, to identify a role for receptor tyrosine kinase inhibitors as modulators of TGFβ signaling.

conclusionThe reporter is a dynamic, noninvasive imaging modality for monitoring TGFβ-induced Smad2 signaling in live cells and tumor xenografts. It has immense potential for identifying novel effectors of R-Smad phosphorylation, for validating drug-target interaction, and for studying TGFβ signaling in different metastasis models.

Indexed as

Signal TransductionAnimalsCell Line, TumorFemaleGenes, ReporterGenes, Tumor SuppressorHigh-Throughput Nucleotide SequencingHigh-Throughput Screening AssaysHumansLuminescent MeasurementsMiceMice, NudeMolecular ImagingPhosphorylationProtein Serine-Threonine KinasesReceptor Protein-Tyrosine KinasesProtein Serine-Threonine KinasesReceptor Protein-Tyrosine KinasesReceptors, Transforming Growth Factor betaReceptor, Transforming Growth Factor-beta Type ISmad2 ProteinSMAD2 protein, humanSmad3 ProteinSMAD3 protein, humanTGFBR1 protein, humanTgfbr1 protein, mouseTransforming Growth Factor beta

Identifiers

PMID21948232
PMCPMC3229686
OpenAlexW2126909043

What OpenQuestion holds

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LicenceTDM
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.