ArticleScience signaling2016
Phosphoproteomic analysis of interacting tumor and endothelial cells identifies regulatory mechanisms of transendothelial migration.
Article in Science signaling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Laryngeal squamous cell carcinoma: a functional "two-hit" model of papillomavirus-Epstein-Barr virus synergistic carcinogenesis.Frontiers in cellular and infection microbiology · 2026Pooled it
- Enrichment of Phosphorylated and Glycosylated MHC Peptides for Mass Spectrometry-Based Neoantigen Analysis.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Proteomics appending a complementary dimension to precision oncotherapy.Computational and structural biotechnology journal · 2024Review
- Exploring a Potential Optimization Route for Peptide Ligands of the Sam Domain from the Lipid Phosphatase Ship2.International journal of molecular sciences · 2024Article
- Transvascular transport of nanocarriers for tumor delivery.Nature communications · 2024Review
- Eph receptors and ephrins in cancer progression.Nature reviews. Cancer · 2024Review
- Downregulation of EphA2 stability by RNF5 limits its tumor-suppressive function in HER2-negative breast cancers.Cell death & disease · 2023Article
- Control of Tumor Progression by Angiocrine Factors.Cancers · 2021Review
- High glucose-induced effects on NaAmerican journal of physiology. Cell physiology · 2021Article
- The Role of the Eph Receptor Family in Tumorigenesis.Cancers · 2021Review
- Calcium and TRPV4 promote metastasis by regulating cytoskeleton through the RhoA/ROCK1 pathway in endometrial cancer.Cell death & disease · 2020Article
- Y772 phosphorylation of EphA2 is responsible for EphA2-dependent NPC nasopharyngeal carcinoma growth by Shp2/Erk-1/2 signaling pathway.Cell death & disease · 2020Article
- Effect of EphA2 knockdown on melanoma metastasis depends on intrinsic ephrinA1 level.Cellular oncology (Dordrecht, Netherlands) · 2020Article
- EPHA2 mutations with oncogenic characteristics in squamous cell lung cancer and malignant pleural mesothelioma.Oncogenesis · 2019Article
- Review
- Proteomics and phosphoproteomics in precision medicine: applications and challenges.Briefings in bioinformatics · 2019Review
- Analyze and Identify Peiminine Target EGFR Improve Lung Function and Alleviate Pulmonary Fibrosis to Prevent Exacerbation of Chronic Obstructive Pulmonary Disease by Phosphoproteomics Analysis.Frontiers in pharmacology · 2019Article
- Article
- Quantitative phosphoproteomic analysis reveals reciprocal activation of receptor tyrosine kinases between cancer epithelial cells and stromal fibroblasts.Clinical proteomics · 2018Article
- The EphA2 receptor is activated through induction of distinct, ligand-dependent oligomeric structures.Communications biology · 2018Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
The exit of metastasizing tumor cells from the vasculature, extravasation, is regulated by their dynamic interactions with the endothelial cells that line the internal surface of vessels. To elucidate signals controlling tumor cell adhesion to the endothelium and subsequent transendothelial migration, we performed phosphoproteomic analysis to map cell-specific changes in protein phosphorylation that were triggered by contact between metastatic MDA-MB-231 breast cancer cells and endothelial cells. From the 2669 unique phosphorylation sites identified, 77 and 43 were differentially phosphorylated in the tumor cells and endothelial cells, respectively. The receptor tyrosine kinase ephrin type A receptor 2 (EPHA2) exhibited decreased Tyr(772) phosphorylation in the cancer cells upon endothelial contact. Knockdown of EPHA2 increased adhesion of the breast cancer cells to human umbilical vein endothelial cells (HUVECs) and their transendothelial migration in coculture cell assays, as well as early-stage lung colonization in vivo. EPHA2-mediated inhibition of transendothelial migration of breast cancer cells depended on interaction with the ligand ephrinA1 on HUVECs and phosphorylation of EPHA2-Tyr(772). When EPHA2 phosphorylation dynamics were compared between cell lines of different metastatic ability, EPHA2-Tyr(772) was rapidly dephosphorylated after ephrinA1 stimulation specifically in cells targeting the lung. Knockdown of the phosphatase LMW-PTP reduced adhesion and transendothelial migration of the breast cancer cells. Overall, cell-specific phosphoproteomic analysis provides a bidirectional map of contact-initiated signaling between tumor and endothelial cells that can be further investigated to identify mechanisms controlling the transendothelial cell migration of cancer cells.
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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.