ArticleMolecular & cellular proteomics : MCP2014
Cross-species proteomics reveals specific modulation of signaling in cancer and stromal cells by phosphoinositide 3-kinase (PI3K) inhibitors.
Article in Molecular & cellular proteomics : MCP, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 27 citations in OpenAlex.
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- Liver Activation of Hepatocellular Nuclear Factor-4α by Small Activating RNA Rescues Dyslipidemia and Improves Metabolic Profile.Molecular therapy. Nucleic acids · 2020Article
- Characterization of four subtypes in morphologically normal tissue excised proximal and distal to breast cancer.NPJ breast cancer · 2020Article
- Dynamic trafficking and turnover of JAM-C is essential for endothelial cell migration.PLoS biology · 2019Article
- Oxidative Stress in Cells with Extra Centrosomes Drives Non-Cell-Autonomous Invasion.Developmental cell · 2018Article
- Post-translational regulation of metabolism in fumarate hydratase deficient cancer cells.Metabolic engineering · 2018Article
- NCK Associated Protein 1 Modulated by miRNA-214 Determines Vascular Smooth Muscle Cell Migration, Proliferation, and Neointima Hyperplasia.Journal of the American Heart Association · 2016Article
- Disulfide-activated protein kinase G Iα regulates cardiac diastolic relaxation and fine-tunes the Frank-Starling response.Nature communications · 2016Article
- Article
- Knockout of the PKN Family of Rho Effector Kinases Reveals a Non-redundant Role for PKN2 in Developmental Mesoderm Expansion.Cell reports · 2016Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The tumor microenvironment plays key roles in cancer biology, but its impact on the regulation of signaling pathway activity in cancer cells has not been systemically investigated. We designed an analytical strategy that allows differential analysis of signaling between cancer and stromal cells present in tumor xenografts. We used this approach to investigate how in vivo growth conditions and PI3K inhibitors regulate pathway activities in both cancer and stromal cell populations. We found that, despite inducing more modest changes in protein expression, in vivo growing conditions extensively rewired protein kinase networks in cancer cells. As a result, different sets of phosphorylation sites were modulated by PI3K inhibitors in cancer cells growing in tumors relative to when these cells were in culture. The p110δ PI3K-selective compound CAL-101 (Idelalisib) did not inhibit markers of PI3K activity in cancer or stromal cells; however, unexpectedly, it induced phosphorylation on SQ motifs in both subpopulations of tumor cells in vivo but not in vitro. Thus, the interaction between cancer cells and the stroma modulated the ability of PI3K inhibitors to induce the activation of apoptosis in solid tumors. Our study provides proof-of-principle of a proteomics workflow for measuring signaling specifically in cancer and stromal cells and for investigating how cancer biochemistry is modulated in vivo.
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