ArticleOncotarget2015
Targeting the degradation of AXL receptor tyrosine kinase to overcome resistance in gefitinib-resistant non-small cell lung cancer.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
46 citing papers in PubMed, 76 citations in OpenAlex.
- Osimertinib Resistance in EGFR-Mutated Non-Small Cell Lung Cancer: Mechanisms and Therapeutic Strategies.MedComm · 2026Review
- Phytochemicals as promising agents in Axl-targeted cancer treatment.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025Review
- Strategies to Overcome Resistance to Osimertinib in EGFR-Mutated Lung Cancer.International journal of molecular sciences · 2025Review
- Bridging the gap: how patient-derived lung cancer organoids are transforming personalized medicine.Frontiers in cell and developmental biology · 2025Review
- Research progress on the role of bypass activation mechanisms in resistance to tyrosine kinase inhibitors in non-small cell lung cancer.Frontiers in oncology · 2024Review
- Nuclear translocation of Axl contributes to the malignancy of oral cancer cells.Journal of dental sciences · 2024Article
- AXL/Gas6 signaling mechanisms in the hypothalamic-pituitary-gonadal axis.Frontiers in endocrinology · 2023Review
- WNK1 collaborates with TGF-β in endothelial cell junction turnover and angiogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Yuanhuacin and Related Anti-Inflammatory and Anticancer Daphnane Diterpenes from Genkwa Flos-An Overview.Biomolecules · 2022Review
- Intrinsic Differences in Spatiotemporal Organization and Stromal Cell Interactions Between Isogenic Lung Cancer Cells of Epithelial and Mesenchymal Phenotypes Revealed by High-Dimensional Single-Cell Analysis of Heterotypic 3D Spheroid Models.Frontiers in oncology · 2022Article
- Targeting MERTK and AXL inCancers · 2021Review
- Therapeutic Targeting of the Gas6/Axl Signaling Pathway in Cancer.International journal of molecular sciences · 2021Review
- The AXL-PYK2-PKCα axis as a nexus of stemness circuits in TNBC.Life science alliance · 2021Article
- Chemotherapy confers a conserved secondary tolerance to EGFR inhibition via AXL-mediated signaling bypass.Scientific reports · 2021Article
- Daphnane-type diterpenes from genusChinese herbal medicines · 2021Review
- Targeting AXL in NSCLC.Lung Cancer (Auckland, N.Z.) · 2021Review
- AXL Mediates Cetuximab and Radiation Resistance Through Tyrosine 821 and the c-ABL Kinase Pathway in Head and Neck Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- AXL Targeting Abrogates Autophagic Flux and Induces Immunogenic Cell Death in Drug-Resistant Cancer Cells.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2020Article
- Single-Cell Proteomic Profiling Identifies Combined AXL and JAK1 Inhibition as a Novel Therapeutic Strategy for Lung Cancer.Cancer research · 2020Article
- Mechanism research of miR-34a regulates Axl in non-small-cell lung cancer with gefitinib-acquired resistance.Thoracic cancer · 2020Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, remains a major problem in non-small cell lung cancer (NSCLC) treatment. Increased activation of AXL has been identified as a novel mechanism for acquired resistance to EGFR-TKIs in NSCLC treatment. However, the cause of uncontrolled AXL expression is not fully understood. Here, we first demonstrate that AXL is overexpressed in an acquired gefitinib-resistant cell line (H292-Gef) as a result of slow turnover and that AXL is degraded by presenilin-dependent regulated intramembrane proteolysis (PS-RIP). Based on the findings, we attempted to enhance AXL degradation to overcome acquired gefitinib-resistance by the treatment of gefitinib-resistant NSCLC cells with yuanhuadine (YD), a potent antitumor agent in NSCLC. Treatment with YD effectively suppressed the cancer cell survival in vitro and in vivo. Mechanistically, YD accelerated the turnover of AXL by PS-RIP and resulted in the down-regulation of the full-length AXL. Therefore, the modulation of the proteolytic process through degradation of overexpressed AXL may be an attractive therapeutic strategy for the treatment of NSCLC and EGFR-TKI-resistant 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.