ArticleJournal of extracellular vesicles2014
Analysis of AKT and ERK1/2 protein kinases in extracellular vesicles isolated from blood of patients with cancer.
Article in Journal of extracellular vesicles, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- Leveraging Quantitative Proteomics and Extracellular Vesicle Data to Uncover Druggable Receptor Kinases Across Cancers.Journal of extracellular vesicles · 2026Article
- Sigma1 inhibitor suppression of adaptive immune resistance mechanisms mediated by cancer cell derived extracellular vesicles.Cancer biology & therapy · 2025Article
- Engineered EVs-Mediated miR-222 Targeting PTEN/FN1 Axis Reverses Anthracycline Resistance in HER2-Negative Breast Cancer.Cancer science · 2025Article
- Extracellular vesicles as biomarkers and drug delivery systems for tumor.Acta pharmaceutica Sinica. B · 2025Review
- Extracellular vesicles in tumor immunity: mechanisms and novel insights.Molecular cancer · 2025Review
- Extracellular vesicles from obese and diabetic mouse plasma alter C2C12 myotube glucose uptake and gene expression.Physiological reports · 2024Article
- Recent advances of small extracellular vesicle biomarkers in breast cancer diagnosis and prognosis.Molecular cancer · 2023Review
- Insulin infusion decreases medium-sized extracellular vesicles in adults with metabolic syndrome.American journal of physiology. Endocrinology and metabolism · 2022Article
- Purification and Phosphoproteomic Analysis of Plasma-Derived Extracellular Vesicles.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Longitudinal stability of urinary extracellular vesicle protein patterns within and between individuals.Scientific reports · 2021Article
- Liquid Biopsy Strategies to Distinguish Progression from Pseudoprogression and Radiation Necrosis in Glioblastomas.Advanced biosystems · 2020Review
- Glass Fiber-Supported Hybrid Monolithic Spin Tip for Enrichment of Phosphopeptides from Urinary Extracellular Vesicles.Analytical chemistry · 2020Article
- EGFR-rich extracellular vesicles derived from highly metastatic nasopharyngeal carcinoma cells accelerate tumour metastasis through PI3K/AKT pathway-suppressed ROS.Journal of extracellular vesicles · 2020Article
- Review
- Role of liquid biopsy in oncogene-addicted non-small cell lung cancer.Translational lung cancer research · 2019Review
- Liquid Biopsy for the Detection of Resistance Mechanisms in NSCLC: Comparison of Different Blood Biomarkers.Journal of clinical medicine · 2019Review
- INKA, an integrative data analysis pipeline for phosphoproteomic inference of active kinases.Molecular systems biology · 2019Article
- Mass spectrometry-based proteome profiling of extracellular vesicles and their roles in cancer biology.Experimental & molecular medicine · 2019Review
- Highly Efficient Phosphoproteome Capture and Analysis from Urinary Extracellular Vesicles.Journal of proteome research · 2018Article
- Quantification and localization of oncogenic receptor tyrosine kinase variant transcripts using molecular inversion probes.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundExtracellular vesicles (EVs) are small nanometre-sized vesicles that are circulating in blood. They are released by multiple cells, including tumour cells. We hypothesized that circulating EVs contain protein kinases that may be assessed as biomarkers during treatment with tyrosine kinase inhibitors.
methodsEVs released by U87 glioma cells, H3255 and H1650 non-small-cell lung cancer (NSCLC) cells were profiled by tandem mass spectrometry. Total AKT/protein kinase B and extracellular signal regulated kinase 1/2 (ERK1/2) levels as well as their relative phosphorylation were measured by western blot in isogenic U87 cells with or without mutant epidermal growth factor receptor (EGFRvIII) and their corresponding EVs. To assess biomarker potential, plasma samples from 24 healthy volunteers and 42 patients with cancer were used.
resultsIn total, 130 different protein kinases were found to be released in EVs including multiple drug targets, such as mammalian target of rapamycin (mTOR), AKT, ERK1/2, AXL and EGFR. Overexpression of EGFRvIII in U87 cells results in increased phosphorylation of EGFR, AKT and ERK1/2 in cells and EVs, whereas a decreased phosphorylation was noted upon treatment with the EGFR inhibitor erlotinib. EV samples derived from patients with cancer contained significantly more protein (p=0.0067) compared to healthy donors. Phosphorylation of AKT and ERK1/2 in plasma EVs from both healthy donors and patients with cancer was relatively low compared to levels in cancer cells. Preliminary analysis of total AKT and ERK1/2 levels in plasma EVs from patients with NSCLC before and after sorafenib/metformin treatment (n=12) shows a significant decrease in AKT levels among patients with a favourable treatment response (p<0.005).
conclusionPhosphorylation of protein kinases in EVs reflects their phosphorylation in tumour cells. Total AKT protein levels may allow monitoring of kinase inhibitor responses in patients with cancer.
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