ArticleExperimental & molecular medicine2013
Phosphoproteomic analysis identifies activated MET-axis PI3K/AKT and MAPK/ERK in lapatinib-resistant cancer cell line.
Article in Experimental & molecular medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 94 citations in OpenAlex.
- Molecular effects of Lapatinib in the treatment of HER2 overexpressing oesophago-gastric adenocarcinoma.British journal of cancer · 2015Trial
- Lapatinib suppresses cysteine deprivation-induced ferroptotic cell death by modulating mitochondrial function.Medical oncology (Northwood, London, England) · 2026Article
- Comprehensive overview of AI methodologies in nano-drug delivery Optimization and Design.NPJ precision oncology · 2026Review
- Anti-RSV drug screening and inhibition of RSV infection by lapatinib through the IL-17 pathway.Antimicrobial agents and chemotherapy · 2026Article
- Lapatinib induces ferroptosis in osteosarcoma via the SLC1A5-GPX4 axis.Journal of bone oncology · 2026Article
- Advanced Phosphoproteomics Depth and Quantitative Performance Using an Integrated noFAIMS-FAIMS Approach.Rapid communications in mass spectrometry : RCM · 2026Article
- Review
- Recent advances in phosphoproteomics based on mass spectrometry and its clinical application prospects.Frontiers in pharmacology · 2026Review
- HER2-positive gastric cancer: from targeted therapy to CAR-T cell therapy.Frontiers in immunology · 2025Review
- Tepotinib for the Treatment of Lung Adenocarcinoma Harboring MET Y1003N Point Mutation: A Case Report.Thoracic cancer · 2025Article
- Evodiamine inhibits proliferation and induces apoptosis of nasopharyngeal carcinoma cells via the SRC/ERBB2-mediated MAPK/ERK signaling pathway.Journal of translational medicine · 2024Article
- HER2-targeted therapies beyond breast cancer - an update.Nature reviews. Clinical oncology · 2024Review
- MST1R-targeted therapy in the battle against gallbladder cancer.Cell & bioscience · 2024Article
- Review
- Principles of phosphoproteomics and applications in cancer research.The Biochemical journal · 2023Article
- Article
- Review
- miR-221 confers lapatinib resistance by negatively regulating p27Cancer science · 2021Article
- A Novel c-Mesenchymal-Epithelial Transition Factor Intergenic Fusion Response to Crizotinib in a Chinese Patient With Lung Adenocarcinoma: A Case Report.Frontiers in oncology · 2021Article
- Recent Advances of Functional Proteomics in Gastrointestinal Cancers- a Path towards the Identification of Candidate Diagnostic, Prognostic, and Therapeutic Molecular Biomarkers.International journal of molecular sciences · 2020Review
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Authors and funding
7 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lapatinib, a dual inhibitor of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) tyrosine kinases, has shown promising results as a growth inhibitor of HER2-positive cancer cells in vitro. However, similar to other EGFR-targeting drugs, acquired resistance to lapatinib by HER2-positive cancer cells remains a major clinical challenge. To elucidate resistance mechanisms to EGFR/HER2-targeting agents, we performed a systematic quantitative comparison of the phosphoproteome of lapatinib-resistant (LR) human gastric cancer cells (SNU216-LR) versus parental cells (SNU216) using a titanium dioxide (TiO2) phosphopeptide enrichment method and analysis with a Q-Exactive hybrid quadrupole-Orbitrap mass spectrometer. Biological network analysis of differentially expressed phosphoproteins revealed apparent constitutive activation of the MET-axis phosphatidylinositide 3-kinase (PI3K)/α-serine/threonine-protein kinase (AKT) and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathways in SNU216-LR. Inhibition of the PI3K/AKT and MAPK/ERK signaling pathways in SNU216-LR also leads to cell cycle arrest, confirming the biological network analysis. Lapatinib sensitivity was restored when cells were treated with several molecular targeting agents in combination with lapatinib. Thus, by integrating phosphoproteomic data, protein networks and effects of signaling pathway modulation on cell proliferation, we found that SNU216-LR maintains constitutive activation of the PI3K/AKT and MAPK/ERK pathways in a MET-dependent manner. These findings suggest that pathway activation is a key compensatory intracellular phospho-signaling event that may govern gastric cancer cell resistance to drug treatment.
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