ArticleMolecular cancer2013
Lyn, a Src family kinase, regulates activation of epidermal growth factor receptors in lung adenocarcinoma cells.
Article in Molecular cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 51 citations in OpenAlex.
- LncRNA EUDAL shapes tumor cell response to hypoxia-induced constitutive EGFR activation and promotes chemoresistance in oral cancer.International journal of oral science · 2025Article
- USP21-EGFR-Lyn axis drives NSCLC progression and therapeutic potential of USP21 inhibition.Biomarker research · 2025Article
- EGFR-to-Src family tyrosine kinase switching in proliferating-DTP TNBC cells creates a hyperphosphorylation-dependent vulnerability to EGFR TKI.Cancer cell international · 2025Article
- Decoding sunitinib resistance in ccRCC: Metabolic-reprogramming-induced ABAT and GABAergic system shifts.iScience · 2024Article
- WISP1 induces the expression of macrophage migration inhibitory factor in human lung fibroblasts through Src kinases and EGFR-activated signaling pathways.American journal of physiology. Cell physiology · 2024Article
- Loss of SMURF2 expression enhances RACK1 stability and promotes ovarian cancer progression.Cell death and differentiation · 2023Article
- Src heterodimerically activates Lyn or Fyn to serve as targets for the diagnosis and treatment of esophageal squamous cell carcinoma.Science China. Life sciences · 2023Article
- DriverMP enables improved identification of cancer driver genes.GigaScience · 2022Article
- ARAF suppresses ERBB3 expression and metastasis in a subset of lung cancers.Science advances · 2022Article
- How to Achieve Therapeutic Response in Erlotinib-Resistant Head and Neck Squamous Cell Carcinoma? New Insights from Stable Isotope Labeling with Amino Acids in Cell Culture-Based Quantitative Tyrosine Phosphoproteomics.Omics : a journal of integrative biology · 2021Article
- STING Mediates Lupus via the Activation of Conventional Dendritic Cell Maturation and Plasmacytoid Dendritic Cell Differentiation.iScience · 2020Article
- Oncogenic role of LYN in human gastric cancer via the Wnt/β-catenin and AKT/mTOR pathways.Experimental and therapeutic medicine · 2020Article
- Identification of 1Journal of enzyme inhibition and medicinal chemistry · 2019Article
- Src kinase inhibitor PP2 regulates the biological characteristics of A549 cells via the PI3K/Akt signaling pathway.Oncology letters · 2018Article
- Inhibition of Epidermal Growth Factor Receptor (EGFR) Reduces Lipopolysaccharide (LPS)-Induced Activation and Inflammatory Cytokines in Hepatic Stellate Cells In Vitro.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- Salidroside inhibits the proliferation and migration of gastric cancer cells via suppression of Src‑associated signaling pathway activation and heat shock protein 70 expression.Molecular medicine reports · 2018Article
- RACK1 Silencing Induces Cell Apoptosis and Inhibits Cell Proliferation in Hepatocellular Carcinoma MHCC97-H Cells.Pathology oncology research : POR · 2018Article
- Honokiol Inhibits Proliferation, Invasion and Induces Apoptosis Through Targeting Lyn Kinase in Human Lung Adenocarcinoma Cells.Frontiers in pharmacology · 2018Article
- Chronic Cigarette Smoke Mediated Global Changes in Lung Mucoepidermoid Cells: A Phosphoproteomic Analysis.Omics : a journal of integrative biology · 2017Article
- Inhibition of epidermal growth factor receptor attenuates LPS-induced inflammation and acute lung injury in rats.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundActivation of receptors for growth factors on lung epithelial cells is essential for transformation into tumor cells, supporting their viability and proliferation. In most lung cancer patients, EGFR is constitutively activated without evidence of mutation. Defining mechanisms for constitutive activation of EGFR could elucidate additional targets for therapy of lung cancers.
methodsThe approach was to identify lung cancer cell lines with constitutively activated EGFR and use systematic selection of inhibitors to evaluate their effects on specific EGFR phosphorylations and downstream signaling pathways. Interactions between receptors, kinases, and scaffolding proteins were investigated by co-immunoprecipitation plus Western blotting.
resultsThe results revealed a dependence on Src family of tyrosine kinases for downstream signaling and cell growth. Lyn, a Src family kinase functional in normal and malignant B-lymphocytes, was a defining signal transducer required for EGFR signaling in Calu3 cell line. Src family kinase activation in turn, was dependent on PKCßII. Lyn and PKC exist in membrane complexes of RACK1 and in association with EGFR which pairs with other receptor partners. Silencing of Lyn expression with interfering siRNA decreased EGFR activation and cell viability.
conclusionsThe importance of Src family kinases and PKCßII in the initiation of the EGFR signaling pathway in lung tumor cells was demonstrated. We conclude that phosphorylation of EGFR is mediated through PKCßII regulation of Lyn activation, and occurs in association with RACK1 and Cbp/PAG proteins. We suggest that protein complexes in cell membranes, including lipid rafts, may serve as novel targets for combination therapies with EGFR and Src Family Kinase inhibitors in lung cancer.
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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.