ArticleGenome biology2009
Integrated analysis of breast cancer cell lines reveals unique signaling pathways.
Article in Genome biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 62 citations in OpenAlex.
- Systems Medicine Design for Triple-Negative Breast Cancer and Non-Triple-Negative Breast Cancer Based on Systems Identification and Carcinogenic Mechanisms.International journal of molecular sciences · 2021Article
- Coordinated dysregulation of cancer progression by the HER family and p21-activated kinases.Cancer metastasis reviews · 2020Review
- Machine Learning for Integrating Data in Biology and Medicine: Principles, Practice, and Opportunities.An international journal on information fusion · 2019Article
- Tumor-stroma interactions differentially alter drug sensitivity based on the origin of stromal cells.Molecular systems biology · 2018Article
- Epidermal Growth Factor Signaling towards Proliferation: Modeling and Logic Inference Using Forward and Backward Search.BioMed research international · 2017Article
- FOXA1 overexpression mediates endocrine resistance by altering the ER transcriptome and IL-8 expression in ER-positive breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- An unbiased metric of antiproliferative drug effect in vitro.Nature methods · 2016Article
- Computational approaches in target identification and drug discovery.Computational and structural biotechnology journal · 2016Review
- Anticancer drug sensitivity prediction in cell lines from baseline gene expression through recursive feature selection.BMC cancer · 2015Article
- Pathway mapping and development of disease-specific biomarkers: protein-based network biomarkers.Journal of cellular and molecular medicine · 2015Review
- In vitro human cell line models to predict clinical response to anticancer drugs.Pharmacogenomics · 2015Review
- Cancer Systems Biology: a peek into the future of patient care?Nature reviews. Clinical oncology · 2014Review
- NF-κB activation-induced anti-apoptosis renders HER2-positive cells drug resistant and accelerates tumor growth.Molecular cancer research : MCR · 2014Article
- Survey of network-based approaches to research of cardiovascular diseases.BioMed research international · 2014Review
- The role of engineering approaches in analysing cancer invasion and metastasis.Nature reviews. Cancer · 2013Review
- Dasatinib synergizes with both cytotoxic and signal transduction inhibitors in heterogeneous breast cancer cell lines--lessons for design of combination targeted therapy.Cancer letters · 2012Article
- Identification of aberrant pathways and network activities from high-throughput data.Briefings in bioinformatics · 2012Review
- Loss of cell-surface laminin anchoring promotes tumor growth and is associated with poor clinical outcomes.Cancer research · 2012Article
- Caveolin-1 expression is elevated in claudin-low mammary tumor cells.Cancer cell international · 2012Article
- Models and Mechanisms of Acquired Antihormone Resistance in Breast Cancer: Significant Clinical Progress Despite Limitations.Hormone molecular biology and clinical investigation · 2012Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundCancer is a heterogeneous disease resulting from the accumulation of genetic defects that negatively impact control of cell division, motility, adhesion and apoptosis. Deregulation in signaling along the EgfR-MAPK pathway is common in breast cancer, though the manner in which deregulation occurs varies between both individuals and cancer subtypes.
resultsWe were interested in identifying subnetworks within the EgfR-MAPK pathway that are similarly deregulated across subsets of breast cancers. To that end, we mapped genomic, transcriptional and proteomic profiles for 30 breast cancer cell lines onto a curated Pathway Logic symbolic systems model of EgfR-MAPK signaling. This model was composed of 539 molecular states and 396 rules governing signaling between active states. We analyzed these models and identified several subtype-specific subnetworks, including one that suggested Pak1 is particularly important in regulating the MAPK cascade when it is over-expressed. We hypothesized that Pak1 over-expressing cell lines would have increased sensitivity to Mek inhibitors. We tested this experimentally by measuring quantitative responses of 20 breast cancer cell lines to three Mek inhibitors. We found that Pak1 over-expressing luminal breast cancer cell lines are significantly more sensitive to Mek inhibition compared to those that express Pak1 at low levels. This indicates that Pak1 over-expression may be a useful clinical marker to identify patient populations that may be sensitive to Mek inhibitors.
conclusionsAll together, our results support the utility of symbolic system biology models for identification of therapeutic approaches that will be effective against breast cancer subsets.
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Registered trials
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.