ArticleMolecular & cellular proteomics : MCP2013
Quantitative proteomics with siRNA screening identifies novel mechanisms of trastuzumab resistance in HER2 amplified breast cancers.
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.
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Who cites it
29 citing papers in PubMed, 47 citations in OpenAlex.
- [Molecular imaging and biology · 2016Trial
- Scalable clinical proteomics from DNA/RNA extraction flowthroughs enables integrated proteogenomic profiling from a single cancer biopsy.Clinical proteomics · 2026Article
- Article
- Potential Biomarkers Associated with Prognosis and Trastuzumab Response in HER2+ Breast Cancer.Cancers · 2023Article
- Involvement of FAM83 Family Proteins in the Development of Solid Tumors: An Update Review.Journal of Cancer · 2023Review
- FAM83A is a potential biomarker for breast cancer initiation.Biomarker research · 2022Article
- Pan-cancer analysis of the FAM83 family and its association with prognosis and tumor microenvironment.Frontiers in genetics · 2022Article
- Impact ofEuropean journal of nuclear medicine and molecular imaging · 2021Article
- Monitoring protein communities and their responses to therapeutics.Nature reviews. Drug discovery · 2020Review
- FAM83A is amplified and promotes tumorigenicity in non-small cell lung cancer via ERK and PI3K/Akt/mTOR pathways.International journal of medical sciences · 2020Article
- Anti-CDCP1 immuno-conjugates for detection and inhibition of ovarian cancer.Theranostics · 2020Article
- A FAM83A Positive Feed-back Loop Drives Survival and Tumorigenicity of Pancreatic Ductal Adenocarcinomas.Scientific reports · 2019Article
- 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 · 2019Article
- FAM83A and FAM83B as Prognostic Biomarkers and Potential New Therapeutic Targets in NSCLC.Cancers · 2019Article
- Applications of RNA Indexes for Precision Oncology in Breast Cancer.Genomics, proteomics & bioinformatics · 2018Review
- Novel small molecule inhibiting CDCP1-PKCδ pathway reduces tumor metastasis and proliferation.Cancer science · 2017Article
- Harnessing Integrative Omics to Facilitate Molecular Imaging of the Human Epidermal Growth Factor Receptor Family for Precision Medicine.Theranostics · 2017Review
- HER2-positive breast cancer cells expressing elevated FAM83A are sensitive to FAM83A loss.PloS one · 2017Article
- Comprehensive molecular tumor profiling in radiation oncology: How it could be used for precision medicine.Cancer letters · 2016Review
- FAM83 proteins: Fostering new interactions to drive oncogenic signaling and therapeutic resistance.Oncotarget · 2016Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
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.
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Registered trials
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