Evidence map›Paper›PMID 23105007›Full record

ArticleMolecular & cellular proteomics : MCP2013

Quantitative proteomics with siRNA screening identifies novel mechanisms of trastuzumab resistance in HER2 amplified breast cancers.

Alaina P Boyer, Timothy S Collier, Ilan Vidavsky, Ron Bose

Open access · hybridAbstract read
In one paragraph

Article in Molecular & cellular proteomics : MCP, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
2.5field-weighted citation impact, top 12% 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

29 citing papers in PubMed, 47 citations in OpenAlex.

  1. [Molecular imaging and biology · 2016
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  8. Impact ofEuropean journal of nuclear medicine and molecular imaging · 2021
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  13. Overexpression of Family with Sequence Similarity 83, Member A (FAM83A) Predicts Poor Clinical Outcomes in Lung Adenocarcinoma.Medical science monitor : international medical journal of experimental and clinical research · 2019
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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.

Alaina P BoyerDivision of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Timothy S Collier
Ilan Vidavsky
Ron Bose
Washington University in St. Louis · US

Funding

YOGA LIFESTYLE INTERVENTION REDUCES BLOOD PRESSURE IN HIV-INFECTED ADULTSP41RR000954 · NCRR · WASHINGTON UNIVERSITY · PI GROSS, MICHAEL L · 1985 to 2011
$16.0M
PRE-AND POSTGRADUATE TRAINING IN MOLECULAR HEMATOLOGYT32HL007088 · NHLBI · WASHINGTON UNIVERSITY · PI Grant Anthony Challen, Stephen Oh · 1985 to 2026
$14.1M
MOLECULAR ONCOLOGY TRAINING GRANTT32CA113275 · NCI · WASHINGTON UNIVERSITY · PI Matthew J Walter · 2006 to 2026
$5.7M
NCI NIH HHS CA113275NCI NIH HHS T32 CA113275NCRR NIH HHS 2P41RR000954NCRR NIH HHS P41 RR000954NHLBI NIH HHS 2T32HL007088-36NHLBI NIH HHS T32 HL007088
6 · The paper itself

Abstract

HER2 is a receptor tyrosine kinase that is overexpressed in 20% to 30% of human breast cancers and which affects patient prognosis and survival. Treatment of HER2-positive breast cancer with the monoclonal antibody trastuzumab (Herceptin) has improved patient survival, but the development of trastuzumab resistance is a major medical problem. Many of the known mechanisms of trastuzumab resistance cause changes in protein phosphorylation patterns, and therefore quantitative proteomics was used to examine phosphotyrosine signaling networks in trastuzumab-resistant cells. The model system used in this study was two pairs of trastuzumab-sensitive and -resistant breast cancer cell lines. Using stable isotope labeling, phosphotyrosine immunoprecipitations, and online TiO(2) chromatography utilizing a dual trap configuration, ~1700 proteins were quantified. Comparing quantified proteins between the two cell line pairs showed only a small number of common protein ratio changes, demonstrating heterogeneity in phosphotyrosine signaling networks across different trastuzumab-resistant cancers. Proteins showing significant increases in resistant versus sensitive cells were subjected to a focused siRNA screen to evaluate their functional relevance to trastuzumab resistance. The screen revealed proteins related to the Src kinase pathway, such as CDCP1/Trask, embryonal Fyn substrate, and Paxillin. We also identify several novel proteins that increased trastuzumab sensitivity in resistant cells when targeted by siRNAs, including FAM83A and MAPK1. These proteins may present targets for the development of clinical diagnostics or therapeutic strategies to guide the treatment of HER2+ breast cancer patients who develop trastuzumab resistance.

Indexed as

Antibodies, Monoclonal, HumanizedAntigens, CDAntigens, NeoplasmBreast NeoplasmsCell Adhesion MoleculesCell Line, TumorCyclin-Dependent KinasesDrug Resistance, NeoplasmErb-b2 Receptor Tyrosine KinasesFemaleHumansIsotope LabelingNeoplasm ProteinsPaxillinPhosphatidylinositol 3-KinasePhosphorylationAntibodies, Monoclonal, HumanizedAntigens, CDAntigens, NeoplasmCDCP1 protein, humanCell Adhesion MoleculesCyclin-Dependent KinasesERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesNeoplasm ProteinsPaxillinPhosphatidylinositol 3-KinasePhosphotyrosineProto-Oncogene Proteins c-aktRNA, Small InterferingTrastuzumab

Identifiers

PMID23105007
PMCPMC3536899
OpenAlexW1999353750

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.