Evidence map›Paper›PMID 23091114›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2012

HER2-associated radioresistance of breast cancer stem cells isolated from HER2-negative breast cancer cells.

Nadire Duru, Ming Fan, Demet Candas, Cheikh Menaa, Hsin-Chen Liu, Danupon Nantajit, Yunfei Wen, Kai Xiao, Angela Eldridge, Brett A Chromy and 5 more

Open access · bronzeAbstract read
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
119citing papers in PubMed, 1 pooled it
6.8field-weighted citation impact, top 2% 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

119 citing papers in PubMed, 1 synthesis or guideline pooled it, 203 citations in OpenAlex.

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  17. Co-injection of anti-HER2 antibody Trastuzumab does not increase efficacy of [American journal of nuclear medicine and molecular imaging · 2023
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59 more citing papers are in PubMed but not listed here.

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

15 authors at 6 institutions in 1 country.

Nadire DuruDepartments of Radiation Oncology, University of California Davis School of Medicine, Sacramento, Ca 95817, USA.
Ming Fan
Demet Candas
Cheikh Menaa
Hsin-Chen Liu
Danupon Nantajit
Yunfei Wen
Kai Xiao
Angela Eldridge
Brett A Chromy
Shiyong Li
Douglas R Spitz
Kit S Lam
Max S Wicha
Jian Jian Li
Lawrence Livermore National Laboratory · USUniversity of Michigan–Ann Arbor · USUniversity of California, Davis · USThe University of Texas MD Anderson Cancer Center · USEmory University · USMichigan Center for Translational Pathology · US

Funding

Staff InvestigatorsP30CA093373 · NCI · UNIVERSITY OF CALIFORNIA DAVIS · PI Laura Marcu · 2002 to 2026
$84.9M
Regulation of Breast Stem Cells by the MicroenvironmentR01CA101860 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WICHA, MAX S. · 2004 to 2013
$2.4M
Target MKP-1 for Therapy-Resistant Breast Cancer Stem CellsR01CA152313 · NCI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI LI, JIAN JIAN · 2011 to 2015
$1.9M
NF-kB-mediated HER-2 overexpression in radioresistant breast cancer stem cells?R01CA133402 · NCI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI LI, JIAN JIAN · 2009 to 2013
$1.5M
The Use of 2-Deoxyglucose in Head and Neck Cancer TherapyR01CA133114 · NCI · UNIVERSITY OF IOWA · PI SPITZ, DOUGLAS ROBERT · 2009 to 2013
$1.5M
NCI NIH HHS CA133114NCI NIH HHS CA133402NCI NIH HHS CA152313NCI NIH HHS P30 CA093373NCI NIH HHS R01 CA101860NCI NIH HHS R01 CA133114NCI NIH HHS R01 CA133402NCI NIH HHS R01 CA152313
6 · The paper itself

Abstract

purposeTo understand the role of HER2-associated signaling network in breast cancer stem cells (BCSC) using radioresistant breast cancer cells and clinical recurrent breast cancers to evaluate HER2-targeted therapy as a tumor eliminating strategy for recurrent HER2(-/low) breast cancers. EXPERIMENTAL

designHER2-expressing BCSCs (HER2(+)/CD44(+)/CD24(-/low)) were isolated from radiation-treated breast cancer MCF7 cells and in vivo irradiated MCF7 xenograft tumors. Tumor aggressiveness and radioresistance were analyzed by gap filling, Matrigel invasion, tumor-sphere formation, and clonogenic survival assays. The HER2/CD44 feature was analyzed in 40 primary and recurrent breast cancer specimens. Protein expression profiling in HER2(+)/CD44(+)/CD24(-/low) versus HER2(-)/CD44(+)/CD24(-/low) BCSCs was conducted with two-dimensional difference gel electrophoresis (2-D DIGE) and high-performance liquid chromatography tandem mass spectrometry (HPLC/MS-MS) analysis and HER2-mediated signaling network was generated by MetaCore program.

resultsCompared with HER2-negative BCSCs, HER2(+)/CD44(+)/CD24(-/low) cells showed elevated aldehyde dehydrogenase (ALDH) activity and aggressiveness tested by Matrigel invasion, tumor sphere formation, and in vivo tumorigenesis. The enhanced aggressive phenotype and radioresistance of the HER2(+)/CD44(+)/CD24(-/low) cells were markedly reduced by inhibition of HER2 via siRNA or Herceptin treatments. Clinical breast cancer specimens revealed that cells coexpressing HER2 and CD44 were more frequently detected in recurrent (84.6%) than primary tumors (57.1%). In addition, 2-D DIGE and HPLC/MS-MS of HER2(+)/CD44(+)/CD24(-/low) versus HER2(-)/CD44(+)/CD24(-/low) BCSCs reported a unique HER2-associated protein profile including effectors involved in tumor metastasis, apoptosis, mitochondrial function, and DNA repair. A specific feature of HER2-STAT3 network was identified.

conclusionThis study provides the evidence that HER2-mediated prosurvival signaling network is responsible for the aggressive phenotype of BCSCs that could be targeted to control the therapy-resistant HER2(-/low) breast cancer.

Indexed as

AnimalsApoptosisBreast NeoplasmsCD24 AntigenCell MovementCell Transformation, NeoplasticErb-b2 Receptor Tyrosine KinasesFemaleGene ExpressionHumansHyaluronan ReceptorsMCF-7 CellsMembrane Potential, MitochondrialMiceMice, Inbred NODMice, NudeCD24 AntigenCD24 protein, humanCD44 protein, humanERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesHyaluronan ReceptorsSTAT3 protein, humanSTAT3 Transcription Factor

Identifiers

PMID23091114
PMCPMC3593096
OpenAlexW2155509815

What OpenQuestion holds

Textmetadata
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.