Evidence map›Paper›PMID 29037858›Full record

ArticleThe American journal of pathology2018

Co-Localization of Insulin-Like Growth Factor Binding Protein-1, Casein Kinase-2β, and Mechanistic Target of Rapamycin in Human Hepatocellular Carcinoma Cells as Demonstrated by Dual Immunofluorescence and in Situ Proximity Ligation Assay.

Sahil S Singal, Karen Nygard, Manthan R Dhruv, Kyle Biggar, Majida A Shehab, Shawn S-C Li, Thomas Jansson, Madhulika B Gupta

Open access · bronzeAbstract read
In one paragraph

Article in The American journal of pathology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.7field-weighted citation impact, top 30% 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

11 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
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  4. Article
  5. Dairy consumption and hepatocellular carcinoma risk.Annals of translational medicine · 2021
    Review
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  10. Observational
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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

8 authors at 4 institutions in 2 countries.

Sahil S SingalDepartment of Biochemistry, University of Western Ontario, London, Ontario, Canada.
Karen NygardBiotron Laboratory, University of Western Ontario, London, Ontario, Canada.
Manthan R DhruvDepartment of Pediatrics, University of Western Ontario, London, Ontario, Canada.
Kyle BiggarDepartment of Biochemistry, University of Western Ontario, London, Ontario, Canada; Institute of Biochemistry, Carleton University, Ottawa, Ontario, Canada.
Majida A ShehabDepartment of Pediatrics, University of Western Ontario, London, Ontario, Canada.
Shawn S-C LiDepartment of Biochemistry, University of Western Ontario, London, Ontario, Canada.
Thomas JanssonDepartment of Obstetrics & Gynecology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, Canada.
Madhulika B GuptaDepartment of Biochemistry, University of Western Ontario, London, Ontario, Canada; Department of Pediatrics, University of Western Ontario, London, Ontario, Canada; Children's Health Research Institute, London, Ontario, Canada. Electronic address: mbgupta@uwo.ca.
Western University · CACarleton University · CAChildren’s Health Research Institute · CAUniversity of Colorado Anschutz Medical Campus · US

Funding

PILOT STUDY--SUBSTRATE METABOLISM IN EXTREMELY LOW BIRTH WEIGHT INFANTSP30DK048520 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI Edward L Melanson · 1995 to 2026
$32.6M
IGFBP-1 hyperphosphorylation in IUGR: Role of mTOR and CK2R03HD078313 · NICHD · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI GUPTA, MADHULIKA, JANSSON, THOMAS · 2014 to 2015
$147k
NICHD NIH HHS R03 HD078313
6 · The paper itself

Abstract

Insulin-like growth factor binding protein (IGFBP)-1 influences fetal growth by modifying insulin-like growth factor-I (IGF-I) bioavailability. IGFBP-1 phosphorylation, which markedly increases its affinity for IGF-I, is regulated by mechanistic target of rapamycin (mTOR) and casein kinase (CSNK)-2. However, the underlying molecular mechanisms remain unknown. We examined the cellular localization and potential interactions of IGFBP-1, CSNK-2β, and mTOR as a prerequisite for protein-protein interaction. Analysis of dual immunofluorescence images indicated a potential perinuclear co-localization between IGFBP-1 and CSNK-2β and a nuclear co-localization between CSNK-2β and mTOR. Proximity ligation assay (PLA) indicated proximity between IGFBP-1 and CSNK-2β as well as mTOR and CSNK-2β but not between mTOR and IGFBP-1. Three-dimensional rendering of the PLA images validated that IGFBP-1 and CSNK-2β interactions were in the perinuclear region and mTOR and CSNK-2β interactions were also predominantly perinuclear rather than nuclear as indicated by mTOR and CSNK-2β co-localization. Compared with control, hypoxia and rapamycin treatment showed markedly amplified PLA signals for IGFBP-1 and CSNK-2β (approximately 18-fold, P = 0.0002). Stable isotope labeling with multiple reaction monitoring-mass spectrometry demonstrated that hypoxia and rapamycin treatment increased IGFBP-1 phosphorylation at Ser98/Ser101/Ser119/Ser174 but most considerably (106-fold) at Ser169. We report interactions between CSNK-2β and IGFBP-1 as well as mTOR and CSNK-2β, providing strong evidence of a mechanistic link between mTOR and IGF-I signaling, two critical regulators of cell growth via CSNK-2.

Indexed as

Carcinoma, HepatocellularCasein Kinase IIFluorescent Antibody TechniqueHep G2 CellsHumansInsulin-Like Growth Factor Binding Protein 1Liver NeoplasmsPhosphorylationSignal TransductionTOR Serine-Threonine KinasesCasein Kinase IIInsulin-Like Growth Factor Binding Protein 1MTOR protein, humanTOR Serine-Threonine Kinases

Identifiers

PMID29037858
PMCPMC5745526
OpenAlexW2769762128

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.