Evidence map›Paper›PMID 31122207›Full record

ArticleBMC cancer2019

Eukaryotic initiation factor 4E-binding protein as an oncogene in breast cancer.

Alexandria C Rutkovsky, Elizabeth S Yeh, Stephen T Guest, Victoria J Findlay, Robin C Muise-Helmericks, Kent Armeson, Stephen P Ethier

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
5.5field-weighted citation impact, top 4% 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

39 citing papers in PubMed, 64 citations in OpenAlex.

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  15. HighAmerican journal of cancer research · 2024
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  20. High expression of autophagy-related geneWorld journal of clinical cases · 2023
    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

7 authors at 3 institutions in 1 country.

Alexandria C RutkovskyDepartment of Pathology and Laboratory Medicine, Medical University of South Carolina, 171 Ashley Avenue, MSC 908, Charleston, SC, 29425, USA.
Elizabeth S YehDepartment of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, 173 Ashley Avenue, BSB 358, MSC 509, Charleston, SC, 29425, USA.
Stephen T GuestDepartment of Computational Medicine and Bioinformatics, University of Michigan, 500 S. State Street, Ann Arbor, MI, 48109, USA.
Victoria J FindlayDepartment of Pathology and Laboratory Medicine, Medical University of South Carolina, 171 Ashley Avenue, MSC 908, Charleston, SC, 29425, USA.
Robin C Muise-HelmericksDepartment of Regenerative Medicine and Cell Biology, Medical University of South Carolina, 173 Ashley Avenue, BSB 601, MSC 508, Charleston, SC, 29425, USA.
Kent ArmesonHollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC, 29425, USA.
Stephen P EthierDepartment of Pathology and Laboratory Medicine, Medical University of South Carolina, 171 Ashley Avenue, MSC 908, Charleston, SC, 29425, USA. ethier@musc.edu.
Medical University of South Carolina · USMUSC Hollings Cancer Center · USUniversity of Michigan–Ann Arbor · US

Funding

Translational Science Laboratory Shared ResourceP30CA138313 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI RAYMOND N. DUBOIS · 2009 to 2026
$42.7M
Breast cancer oncogenes on the 8p11 amplicon.R01CA100724 · NCI · WAYNE STATE UNIVERSITY · PI ETHIER, STEPHEN P. · 2003 to 2014
$3.5M
Breast cancer oncogenes on the 8p11 ampliconR56CA100724 · NCI · WAYNE STATE UNIVERSITY · PI ETHIER, STEPHEN P. · 2009 to 2009
$352k
National Cancer Institute CA100724NCI NIH HHS P30 CA138313NCI NIH HHS R01 CA100724NCI NIH HHS R56 CA100724
6 · The paper itself

Abstract

backgroundEukaryotic Initiation Factor 4E-Binding Protein (EIF4EBP1, 4EBP1) is overexpressed in many human cancers including breast cancer, yet the role of 4EBP1 in breast cancer remains understudied. Despite the known role of 4EBP1 as a negative regulator of cap-dependent protein translation, 4EBP1 is predicted to be an essential driving oncogene in many cancer cell lines in vitro, and can act as a driver of cancer cell proliferation. EIF4EBP1 is located within the 8p11-p12 genomic locus, which is frequently amplified in breast cancer and is known to predict poor prognosis and resistance to endocrine therapy.

methodsHere we evaluated the effect of 4EBP1 targeting using shRNA knock-down of expression of 4EBP1, as well as response to the mTORC targeted drug everolimus in cell lines representing different breast cancer subtypes, including breast cancer cells with the 8p11-p12 amplicon, to better define a context and mechanism for oncogenic 4EBP1.

resultsUsing a genome-scale shRNA screen on the SUM panel of breast cancer cell lines, we found 4EBP1 to be a strong hit in the 8p11 amplified SUM-44 cells, which have amplification and overexpression of 4EBP1. We then found that knock-down of 4EBP1 resulted in dramatic reductions in cell proliferation in 8p11 amplified breast cancer cells as well as in other luminal breast cancer cell lines, but had little or no effect on the proliferation of immortalized but non-tumorigenic human mammary epithelial cells. Kaplan-Meier analysis of EIF4EBP1 expression in breast cancer patients demonstrated that overexpression of this gene was associated with reduced relapse free patient survival across all breast tumor subtypes.

conclusionsThese results are consistent with an oncogenic role of 4EBP1 in luminal breast cancer and suggests a role for this protein in cell proliferation distinct from its more well-known role as a regulator of cap-dependent translation.

Indexed as

OncogenesAdaptor Proteins, Signal TransducingBreast NeoplasmsCell Cycle CheckpointsCell Cycle ProteinsCell ProliferationChromosomes, Human, Pair 8Disease-Free SurvivalEverolimusFemaleGene AmplificationGene Knockdown TechniquesHumansKaplan-Meier EstimateMCF-7 CellsPhosphoproteinsAdaptor Proteins, Signal TransducingCell Cycle ProteinsEIF4EBP1 protein, humanEverolimusMTOR protein, humanPhosphoproteinsReceptors, EstrogenTOR Serine-Threonine Kinases4E-BP14EBP18p11–128p11-p128p12–11AmplificationBreast cancerChromosomal abnormalityDriverEIF4EBP1Estrogen receptorOncogenePHAS-I

Identifiers

PMID31122207
PMCPMC6533768
OpenAlexW2947561691

What OpenQuestion holds

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LicenceCC BY
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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.