ArticleScience signaling2013
The receptor AXL diversifies EGFR signaling and limits the response to EGFR-targeted inhibitors in triple-negative breast cancer cells.
Article in Science signaling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 182 papers, 1 of them a synthesis that pooled it.
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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
182 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- The translational chasm in machine learning for triple-negative breast cancer: a quantitative landscape assessment.Frontiers in oncology · 2026Pooled it
- Targeting the EpCAM-AXL axis to overcome drug resistance in lung cancer.Molecular oncology · 2026Article
- AXL is associated with STAT3 activation in breast cancer.Molecular and clinical oncology · 2026Article
- Window-of-Opportunity Study Utilizing Preoperative Cetuximab in Patients with Head and Neck Cancer.Cancer research communications · 2026Article
- AXL phosphosite mapping links FAK1 and YAP1 signaling to erlotinib resistance in EGFR-mutant lung cancer.Cell reports · 2026Article
- Molecular Mechanisms Underlying Recurrence in Triple-Positive Breast Cancer (ER+/PR+/HER2+) and Potential Repurposing of Multi-Target Inhibitors.International journal of molecular sciences · 2026Review
- Structure-Based Drug Discovery of Triazine Derivatives as Potent and Orally Bioavailable AXL Inhibitors for Cancer Therapy.ACS omega · 2026Article
- The resistance landscape of EGFR tyrosine kinase inhibitors in advanced non-small cell lung cancer: molecular mechanisms and novel therapeutic strategies.Translational lung cancer research · 2026Review
- [Role of Receptor Tyrosine Kinase AXL in Cancer Targeted Therapy Drug Resistance].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Review
- Therapeutic potential of TAM receptors in autoimmune diseases: insights from original studies.Oxford open immunology · 2026Review
- Building a dynamic model for EGFR-family dimerization using quantitative, live-cell fluorescence methods.Biophysical journal · 2025Review
- Targeted Therapies Modulating Mesenchymal-Epithelial Transition-Linked Oncogenic Signaling in the Tumor Microenvironment: Comparative Profiling of Capmatinib, Bemcentinib, and Galunisertib.Journal of clinical medicine · 2025Review
- The Receptor Tyrosine Kinase Axl in (Advanced) Gastric Cancer-From Pathophysiology to Therapeutic Impact.Medicina (Kaunas, Lithuania) · 2025Review
- Review
- Targeting rapid TKI-induced AXL upregulation overcomes adaptive ERK reactivation and exerts antileukemic effects in FLT3/ITD acute myeloid leukemia.Molecular oncology · 2025Article
- AXL signaling in cancer: from molecular insights to targeted therapies.Signal transduction and targeted therapy · 2025Review
- Axl inhibitor-mediated reprogramming of the myeloid compartment of theFrontiers in immunology · 2025Article
- The Biological Roles and Clinical Applications of the PI3K/AKT Pathway in Targeted Therapy Resistance in HER2-Positive Breast Cancer: A Comprehensive Review.International journal of molecular sciences · 2024Review
- From Bench to Bedside: A Team's Approach to Multidisciplinary Strategies to Combat Therapeutic Resistance in Head and Neck Squamous Cell Carcinoma.Journal of clinical medicine · 2024Review
- AXL as immune regulator and therapeutic target in Acute Myeloid Leukemia: from current progress to novel strategies.Experimental hematology & oncology · 2024Review
122 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The relationship between drug resistance, changes in signaling, and emergence of an invasive phenotype is well appreciated, but the underlying mechanisms are not well understood. Using machine learning analysis applied to the Cancer Cell Line Encyclopedia database, we identified expression of AXL, the gene that encodes the epithelial-to-mesenchymal transition (EMT)-associated receptor tyrosine kinase (RTK) AXL, as exceptionally predictive of lack of response to ErbB family receptor-targeted inhibitors. Activation of EGFR (epidermal growth factor receptor) transactivated AXL, and this ligand-independent AXL activity diversified EGFR-induced signaling into additional downstream pathways beyond those triggered by EGFR alone. AXL-mediated signaling diversification was required for EGF (epidermal growth factor)-elicited motility responses in AXL-positive TNBC (triple-negative breast cancer) cells. Using cross-linking coimmunoprecipitation assays, we determined that AXL associated with EGFR, other ErbB receptor family members, MET (hepatocyte growth factor receptor), and PDGFR (platelet-derived growth factor receptor) but not IGF1R (insulin-like growth factor 1 receptor) or INSR (insulin receptor). From these AXL interaction data, we predicted AXL-mediated signaling synergy for additional RTKs and validated these predictions in cells. This alternative mechanism of receptor activation limits the use of ligand-blocking therapies and indicates against therapy withdrawal after acquired resistance. Further, subadditive interaction between EGFR- and AXL-targeted inhibitors across all AXL-positive TNBC cell lines may indicate that increased abundance of EGFR is principally a means to transactivation-mediated signaling.
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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.