ArticleJournal of hematology & oncology2020
Abnormally activated OPN/integrin αVβ3/FAK signalling is responsible for EGFR-TKI resistance in EGFR mutant non-small-cell lung cancer.
Article in Journal of hematology & oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 157 citations in OpenAlex.
- Phase II Study of Defactinib (VS6063) in Patients With Tumors WithJCO precision oncology · 2024Trial
- Synergistic Regulation of Tumor Immunity by Integrins and Lectins: From Molecular Mechanisms to Dual-Targeted Therapy.International journal of molecular sciences · 2026Review
- Osteopontin Promotes Lung Cancer Growth through NF-κB-Dependent Upregulation of PD-L1 and Suppression of Anti-Tumor Immunity.Molecular biology reports · 2026Article
- CCR7-PERK-CREB3L1 signaling mediates tumor-associated macrophages-derived SPP1 promotion of oral squamous cell carcinoma.Communications biology · 2026Article
- Lipid Metabolism, Lipogenesis, and Resistance to Third Generation EGFR-TKIs.Journal of clinical laboratory analysis · 2026Review
- Role of Organ-Specific Endothelial Cells in Melanoma Adhesion Patterns.Biomedicines · 2026Article
- Drug resistant cancer cells show increased nuclear mechanotransduction and mechanically targetable YAP-regulated vulnerability.Biomaterials · 2026Article
- USP20 governs tyrosine kinase inhibitors resistance through ferroptosis evasion by targeting GPX4 in cancers.Redox biology · 2026Article
- Gemcitabine-induced β4 integrin drives cancer progression and gemcitabine resistance in pancreatic cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- FNDC1 is closely related to poor prognosis and immune cell infiltration in gastric cancer.Scientific reports · 2026Article
- Non-enzymatic function of QSOX2 directly regulates the JUNB-ITGB4 axis and enhanced resistance to osimertinib in EGFR-mutation lung adenocarcinoma.Cell death discovery · 2026Article
- [Tumor-secreted dentin sialophosphoprotein induces oxaliplatin resistance in colorectal cancer through an integrin αvβ3-dependent pathway].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- Targeting ABCA3 impedes tumor progression and EGFR-TKI resistance in EGFR-mutant LUAD.Cancer cell international · 2026Article
- DNAJB6 as an immuno-oncogenic hub in liver hepatocellular carcinoma: multi-omic profiling reveals prognostic significance and therapeutic vulnerability.Journal of molecular histology · 2026Article
- Brucein D suppresses breast cancer proliferation and migration via targeting the FAK/LRG1 signaling pathway.Scientific reports · 2025Article
- The crucial role of SPP1 in osteoporosis, osteoarthritis, and cancer.Pharmaceutical science advances · 2025Review
- Targeted drug conjugates and molecular mechanisms in overcoming lung cancer drug resistance.Discover oncology · 2025Review
- EVI5 unveils a role of the oncogene in modulating the Rab11/PD-L1 pathway in lung adenocarcinoma.Scientific reports · 2025Article
- Nanodynamic therapy for cancer: mechanistic innovations, targeting strategies and multimodal treatments.Journal of translational medicine · 2025Review
- Role of osteopontin in cancer: From pathogenesis to therapeutics (Review).Oncology reports · 2025Review
20 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundAcquired epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance limits the long-term clinical efficacy of tyrosine kinase-targeting drugs. Although most of the mechanisms of acquired EGFR-TKI resistance have been revealed, the mechanism of ~ 15% of cases has not yet been elucidated.
methodsCell viability was analysed using the Cell Counting Kit-8 (CCK-8) assay. Proteome profiler array analysis was performed to find proteins contributing to acquired EGFR-TKI resistance. Secreted OPN was detected by ELISA. Immunohistochemical analysis was conducted to detect expression of integrin αV in NSCLC tissue. The effect of VS-6063 on apoptosis and proliferation of PC9 gefitinib-resistant cells was detected by fluorescence-activated cell sorting (FACS) and clonogenic assays. A mouse xenograft model was used to assess the effect of VS-6063 on the sensitivity of PC9 gefitinib-resistant cells to gefitinib.
resultsOPN was overexpressed in acquired EGFR-TKI-resistant NSCLCs. Secreted OPN contributed to acquired EGFR-TKI resistance by activating the integrin αVβ3/FAK pathway. Inhibition of FAK signalling increased sensitivity to EGFR-TKIs in PC9 gefitinib-resistant cells both in vitro and in vivo.
conclusionsOPN contributes to acquired EGFR-TKI resistance by up-regulating expression of integrin αVβ3, which activates the downstream FAK/AKT and ERK signalling pathways to promote cell proliferation in NSCLC.
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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.