Evidence map›Paper›PMID 27694692›Full record

ArticleOncotarget2016

Inhibition of insulin-like growth factor II (IGF-II)-dependent cell growth by multidentate pentamannosyl 6-phosphate-based ligands targeting the mannose 6-phosphate/IGF-II receptor.

Megan E Zavorka, Christopher M Connelly, Rosslyn Grosely, Richard G MacDonald

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2016. 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
0.7field-weighted citation impact, top 24% 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. Directed evolution of genetically encoded LYTACs for cell-mediated delivery.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
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  5. Article
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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 1 institution in 1 country.

Megan E ZavorkaDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA.
Christopher M ConnellyDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA.
Rosslyn GroselyDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA.
Richard G MacDonaldDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA.
University of Nebraska Medical Center · US

Funding

Research Pilot Project ProgramP30GM106397 · NIGMS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI JOHNSON, KEITH R · 2013 to 2017
$4.9M
Nebraska Center for Cellular SignalingP20GM103489 · NIGMS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI JOHNSON, KEITH R · 2012 to 2012
$2.0M
Molecular Dissection of IGF2R Growth Suppressor ActivityR01CA091885 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI MACDONALD, RICHARD G. · 2001 to 2004
$659k
IGF-II-Based Approach to Therapy for Pancreatic CancerR21CA198292 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI MACDONALD, RICHARD G. · 2015 to 2016
$359k
NCI NIH HHS R01 CA091885NCI NIH HHS R21 CA198292NIGMS NIH HHS P20 GM103489NIGMS NIH HHS P30 GM106397
6 · The paper itself

Abstract

The mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF2R) binds M6P-capped ligands and IGF-II at different binding sites within the ectodomain and mediates ligand internalization and trafficking to the lysosome. Multivalent M6P-based ligands can cross-bridge the M6P/IGF2R, which increases the rate of receptor internalization, permitting IGF-II binding as a passenger ligand and subsequent trafficking to the lysosome, where the IGF-II is degraded. This unique feature of the receptor may be exploited to design novel therapeutic agents against IGF-II-dependent cancers that will lead to decreased bioavailable IGF-II within the tumor microenvironment. We have designed a panel of M6P-based ligands that bind to the M6P/IGF2R with high affinity in a bivalent manner and cause decreased cell viability. We present evidence that our ligands bind through the M6P-binding sites of the receptor and facilitate internalization and degradation of IGF-II from conditioned medium to mediate this cellular response. To our knowledge, this is the first panel of synthetic bivalent ligands for the M6P/IGF2R that can take advantage of the ligand-receptor interactions of the M6P/IGF2R to provide proof-of-principle evidence for the feasibility of novel chemotherapeutic agents that decrease IGF-II-dependent growth of cancer cells.

Indexed as

AnimalsAntineoplastic AgentsCell Line, TumorCell ProliferationCell SurvivalHumansInsulin-Like Growth Factor IILigandsLysosomesMannosephosphatesMiceMolecular StructureNeoplasmsProtein MultimerizationProteolysisReceptor, IGF Type 2Antineoplastic AgentsIGF2 protein, humanInsulin-Like Growth Factor IILigandsMannosephosphatesReceptor, IGF Type 2apoptosisbiochemistryinsulin-like growth factorsreceptor

Identifiers

PMID27694692
PMCPMC5308735
OpenAlexW2516192421

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.