Affinage

AXL

Tyrosine-protein kinase receptor UFO · UniProt P30530

Length
894 aa
Mass
98.3 kDa
Annotated
2026-06-09
100 papers in source corpus 32 papers cited in narrative 32 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AXL is a receptor tyrosine kinase that couples extracellular recognition of the ligand Gas6 to intracellular survival, migration, and inflammatory signaling, and is recurrently co-opted in cancer and viral entry (PMID:16362042, PMID:9178760). Its ectodomain is built from two immunoglobulin-like and two fibronectin type III repeats (PMID:1320243), and the crystal structure of the Gas6/Axl complex shows that a single Gas6 laminin G-like domain crosslinks two Axl Ig domains to form a 2:2 assembly through both a major and a minor binding site, productive transmembrane signaling requiring both (PMID:16362042); sequestering Gas6 with an affinity-matured Axl decoy is sufficient to abrogate Axl signaling and block metastasis (PMID:25242553). Activated AXL presents a multi-substrate docking site at phosphotyrosine 821 that recruits PLCγ1, the p85 subunits of PI3K, GRB2, c-Src, and Lck (PMID:9178760), driving PI3K/AKT-dependent cell survival (PMID:16627783) and proliferative signaling (PMID:14729616). Downstream, AXL phosphorylates a NEDD9→CRKII→PEAK1→CSK→PAXILLIN focal-adhesion network to accelerate adhesion turnover and metastasis (PMID:32681075), regulates lysosome positioning and cathepsin B secretion via AKT-NF-κB-MCT-1 control of extracellular acidification to promote invasion (PMID:30189359), and represses TP53 by binding directly to its promoter (PMID:32992696). AXL expression is amplified transcriptionally through EGFR-MAPK-c-Jun feedback (PMID:25136066) and JNK→AP-1 (c-JUN/c-FOS) signaling (PMID:30860495), and AXL serves as a bypass kinase conferring resistance to cetuximab (PMID:25136066) and osimertinib through an AXL/CDCP1/SRC axis (PMID:35643725). AXL protein abundance is set by competing degradation pathways: the LZTR1-CUL3 ubiquitin ligase targets AXL for lysosomal degradation (PMID:36445254), while p85β via TRIM2/optineurin-dependent autophagy (PMID:32385243) and TRIM21-mediated K63 ubiquitination reversed by STAMBPL1 (PMID:39527690) further tune its stability and surface levels. In immune and tissue contexts, AXL acts as a phosphatidylserine receptor—enhanced by phosphatidylethanolamine co-recognition (PMID:33115868)—to drive macropinocytic entry of Ebola and African swine fever virus (PMID:21047970, PMID:37382521), promotes Gas6-driven microglial efferocytosis through Rac1 (PMID:36324028), and reprograms macrophage inflammation via TLR4 cross-talk and STAT1-dependent polarization (PMID:33529176, PMID:37223093). AXL additionally maintains apoE homeostasis in astrocytes independently of its kinase activity (PMID:32366277).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 1992 Medium

    Establishing the molecular identity and domain architecture of Axl defined it as a novel receptor tyrosine kinase with an Ig/fibronectin-III ectodomain expressed in mesodermal tissues, providing the structural foundation for all subsequent ligand and signaling studies.

    Evidence Molecular cloning, sequence comparison, and RNA in situ hybridization of murine Ufo/Axl

    PMID:1320243

    Open questions at the time
    • Ligand and downstream signaling not yet known
    • Functional role of the kinase domain undefined at this stage
  2. 1997 High

    Mapping the cytoplasmic docking sites answered how AXL transmits signal, showing that phosphotyrosine 821 is a multi-substrate platform recruiting PI3K, PLCγ1, GRB2, Src, and Lck, linking the receptor to canonical survival and proliferation cascades.

    Evidence Far-Western, Co-IP, competitive inhibition, and mutagenesis of chimeric EGFR/Ufo receptors

    PMID:9178760

    Open questions at the time
    • Relative in vivo contribution of each docking partner not resolved
    • Did not address ligand-induced activation in native receptor
  3. 2005 High

    The Gas6/Axl crystal structure resolved the mechanism of receptor activation, demonstrating a 2:2 ligand-crosslinked dimer with no direct receptor-receptor contacts and a two-step assembly requiring both major and minor binding sites for productive signaling.

    Evidence X-ray crystallography (3.3 Å) with structure-based mutagenesis and receptor activation assays

    PMID:16362042

    Open questions at the time
    • Dynamics of the two-step dimerization in cells not directly observed
    • Does not address phosphatidylserine-dependent activation modes
  4. 2014 High

    Two complementary 2014 studies established AXL both as a druggable node—Gas6 sequestration via an engineered decoy blocks metastasis—and as a transcriptionally amplified resistance driver under EGFR-MAPK-c-Jun control, linking ligand dependence to therapy resistance.

    Evidence Protein engineering with in vivo metastasis models; RNAi, overexpression, Co-IP, and xenografts in cetuximab-resistant NSCLC/HNSCC

    PMID:25136066 PMID:25242553

    Open questions at the time
    • Decoy efficacy across tumor types not exhaustively mapped
    • Whether all resistance settings depend on Gas6 versus ligand-independent activation unresolved
  5. 2020 High

    Defining the NEDD9→CRKII→PEAK1→CSK→PAXILLIN axis answered how AXL drives invasion mechanistically, showing it accelerates focal-adhesion disassembly to promote metastasis independent of primary tumor growth, alongside chromatin-level TP53 repression and kinase-independent apoE maintenance.

    Evidence Phosphoproteomics, Co-IP, RNAi and in vivo metastasis models; ChIP-qPCR; kinase-dead reconstitution in astrocytoma cells

    PMID:32366277 PMID:32681075 PMID:32992696

    Open questions at the time
    • How AXL accesses the nucleus to bind the TP53 promoter is unclear
    • Mechanism of kinase-independent apoE regulation undefined
  6. 2023 High

    Identifying LZTR1-CUL3, p85β/TRIM2/optineurin autophagy, and TRIM21/STAMBPL1 K63-ubiquitination established that AXL abundance is governed by multiple competing degradation routes, explaining AXL accumulation in LZTR1-mutant tumors and its therapeutic vulnerability.

    Evidence Biochemical screens, Co-IP, ubiquitination assays, conditional mouse KO; phosphorylation/autophagy assays; K63-linkage-specific ubiquitination assays

    PMID:32385243 PMID:36445254 PMID:39527690

    Open questions at the time
    • How these degradation pathways are coordinated or prioritized is unknown
    • Upstream signals triggering each route not defined
  7. 2023 Medium

    Demonstrating AXL as the principal phosphatidylserine receptor for macropinocytic viral entry (Ebola, ASFV), enhanced by phosphatidylethanolamine co-recognition, unified its role in apoptotic-mimicry virus uptake and physiological efferocytosis.

    Evidence RNAi screening, AXL knockout, kinase-domain deletion, R428 inhibition, liposome binding, and live/pseudovirus assays

    PMID:21047970 PMID:33115868 PMID:37382521

    Open questions at the time
    • Whether kinase activity is required for entry differs across systems
    • Mechanism coupling PS binding to macropinocytic machinery incomplete
  8. 2023 Medium

    Multiple immune-context studies established AXL as a regulator of macrophage and microglial inflammatory state, driving STAT1/HIF-1α-dependent M1 polarization, Rac1-dependent efferocytosis, and TLR4-coupled glycolytic reprogramming.

    Evidence Conditional myeloid genetic models, STAT1 siRNA epistasis, R428 inhibition, recombinant Gas6, and disease models (MI/R, SAH, TBI, aneurysm)

    PMID:33529176 PMID:34233703 PMID:36324028 PMID:37223093

    Open questions at the time
    • Context-dependent pro- versus anti-inflammatory outcomes not reconciled
    • Ligand dependence in each immune setting variable

Open questions

Synthesis pass · forward-looking unresolved questions
  • How AXL switches between kinase-dependent oncogenic signaling, ligand-independent activation, and nuclear/transcriptional functions in a context-specific manner remains unresolved.
  • No unified model integrating surface signaling with reported chromatin binding
  • Determinants selecting among competing degradation pathways unknown
  • Mechanism of kinase-independent functions undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0001618 virus receptor activity 2 GO:0008289 lipid binding 2 GO:0016740 transferase activity 2 GO:0048018 receptor ligand activity 2 GO:0060089 molecular transducer activity 2 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005886 plasma membrane 3 GO:0005634 nucleus 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-5653656 Vesicle-mediated transport 2
Partners
CDCP1EGFRGAS6GRB2LZTR1PIK3R2PROS1SRC

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 Crystal structure of the Gas6/Axl complex at 3.3 Å resolution reveals a 2:2 stoichiometry in which the two immunoglobulin-like domains of the Axl ectodomain are crosslinked by the first laminin G-like domain of Gas6, with no direct Axl/Axl or Gas6/Gas6 contacts. Structure-based mutagenesis and receptor activation experiments demonstrated that both a major and minor Gas6-binding site on Axl are required for productive transmembrane signaling. Gas6-mediated Axl dimerization is proposed to occur in two steps, with a high-affinity 1:1 Gas6/Axl complex forming first. X-ray crystallography (3.3 Å), structure-based mutagenesis, protein binding assays, receptor activation experiments The EMBO journal High 16362042
1997 The cytoplasmic domain of Ufo/Axl contains a multi-substrate docking site at C-terminal tyrosine 821 (EILpYVNMDEG) that recruits PLCγ1, p85α and p85β subunits of PI3-kinase, GRB2, c-Src, and Lck. Tyrosine 779 provides an additional lower-affinity docking site for p85 proteins in vitro, and tyrosine 866 is an additional binding site for PLCγ. Identified using far-Western blot, co-immunoprecipitation, competitive inhibition, and mutagenesis of chimeric EGFR/Ufo receptors. Far-Western blot, co-immunoprecipitation, competitive inhibition assays, site-directed mutagenesis of chimeric EGFR/Ufo constructs Oncogene High 9178760
2014 AXL activation in cetuximab-resistant (CtxR) NSCLC and HNSCC cells stimulates cell proliferation, EGFR activation, and MAPK signaling. AXL was found tightly associated with EGFR in CtxR cells, and EGFR directly regulated AXL mRNA expression through MAPK signaling and the transcription factor c-Jun, creating a positive feedback loop. Overexpression of AXL or stimulation with EGFR ligands was sufficient to confer cetuximab resistance. RNAi knockdown, AXL-targeting agents, stable overexpression, co-immunoprecipitation (AXL-EGFR association), mRNA expression analysis, tumor xenograft models Cancer research High 25136066
2014 An engineered Axl 'decoy receptor' with four mutations in the Gas6-binding interface binds Gas6 with femtomolar affinity (80-fold improvement over wild-type), sequesters Gas6, and specifically abrogates Axl signaling. The Fc-fusion decoy receptor potently inhibited metastasis and disease progression in vivo, demonstrating that Gas6 sequestration is sufficient to block Axl pathway activity. Rational and combinatorial protein engineering, binding affinity assays, in vitro Axl signaling inhibition assays, in vivo metastasis models Nature chemical biology High 25242553
2020 AXL stimulates phosphorylation of a focal adhesion (FA) protein network to accelerate FA disassembly and promote cell migration and metastasis. Mechanistically, AXL phosphorylates NEDD9, which binds CRKII, which associates with and orchestrates phosphorylation of pseudo-kinase PEAK1; PEAK1 is in complex with tyrosine kinase CSK to mediate phosphorylation of PAXILLIN. Uncoupling PEAK1 from AXL signaling decreases metastasis in vivo without affecting tumor growth. Phosphoproteomic profiling, co-immunoprecipitation, RNAi knockdown, in vivo metastasis models Nature communications High 32681075
2010 Axl enhances macropinocytosis of Zaire ebolavirus (ZEBOV) in permissive cells. RNAi reduction of Axl expression decreased ZEBOV entry via macropinocytosis but had no effect on clathrin-dependent or caveola/lipid raft-mediated endocytic pathways, demonstrating a specific role for Axl in promoting macropinocytosis-dependent viral entry. Biochemical inhibitors, RNAi knockdown, dominant-negative constructs, viral transduction assays, dextran uptake assays Journal of virology High 21047970
2018 PROS1 (Protein S), secreted by tumor-associated macrophages/microglia, physically associates with and activates AXL in mesenchymal glioblastoma stem cells, leading to NF-κB activation. This PROS1-AXL signaling was inhibited by the small molecule AXL inhibitor BGB324. Co-immunoprecipitation (PROS1-AXL association), pharmacological inhibition, NF-κB pathway readouts, mouse GBM survival models Cancer research Medium 29531161
2006 Axl deficiency (Axl-/- mice) leads to significantly smaller intima+media following carotid artery ligation compared to wild-type, associated with increased apoptosis (5-fold increase in Axl-/- LCA) and decreased p-Akt, demonstrating that Axl mediates flow-dependent vascular remodeling by regulating vascular cell survival through the Akt pathway. Axl knockout mouse model (Axl-/-), carotid ligation model, quantitative immunohistochemistry, apoptosis assays, Western blot for p-Akt Circulation research Medium 16627783
2003 Axl is active in confluent pericytes and its activation by endogenous Gas6 inhibits osteogenic differentiation. Addition of recombinant Axl extracellular domain (ECD) to pericyte cultures inhibited Axl phosphorylation by Gas6 and enhanced the rate of nodule mineralization, demonstrating that Gas6-Axl signaling suppresses the osteogenic differentiation pathway in vascular pericytes. Immunoprecipitation of phosphotyrosine (Axl activity), recombinant Axl-ECD competition assay, Western blot, nodule mineralization assays Circulation research Medium 12730092
1999 E1A negatively regulates Axl expression at the transcriptional level. Gas6 stimulation of Axl in E1A-expressing cells overexpressing Axl provided greater mitogenic effect and protected cells from serum deprivation-induced apoptosis, demonstrating that downregulation of Axl by E1A contributes to E1A-mediated growth suppression and pro-apoptotic activity. RT-PCR tyrosine kinase profiling, cDNA transfection/overexpression, Gas6 stimulation, BrdU incorporation, trypan blue exclusion (survival assay) Molecular and cellular biology Medium 10567533
2004 Gas6 stimulation of Axl in uveal melanoma cells (Mel 290) mediates mitogenesis and cell survival, demonstrated specifically through Axl by antisense-mediated knockdown of Axl expression. Gas6/Axl activation results primarily in downregulation of Cyr61 (a CCN family member) as revealed by cDNA microarray analysis of 12,687 genes. BrdU incorporation, trypan blue exclusion, antisense knockdown, cDNA microarray (12,687 genes) Cancer research Medium 14729616
2021 Cross-signaling between AXL and TLR4 in cardiac macrophages directs a switch to glycolytic metabolism and secretion of proinflammatory IL-1β, leading to increased intramyocardial inflammation, adverse ventricular remodeling, and impaired contractile function after myocardial ischemia/reperfusion injury. AXL functions independently of cardioprotective MerTK, and like MerTK, undergoes proteolytic cleavage. Conditional genetic loss/gain-of-function (myeloid-specific), flow cytometry, metabolic assays, cytokine measurements, cardiac functional readouts The Journal of clinical investigation Medium 33529176
2022 Gas6 promotes microglial efferocytosis and suppresses post-SAH inflammation through activating the Axl/Rac1 signaling pathway. Inhibition or knockdown of Axl or Rac1 abolished the beneficial effects of recombinant Gas6, demonstrating a functional Gas6→Axl→Rac1 signaling axis in microglia efferocytosis. Mouse SAH model, intraventricular injection of recombinant Gas6/ProS1, TAM receptor knockdown (siRNA), specific inhibitors, flow cytometry, in vitro phagocytosis assays Translational stroke research Medium 36324028
2021 AXL activates the STAT1 pathway in astrocytes post-traumatic brain injury, which further upregulates ABCA1, promoting a phagocytic astrocyte phenotype (AXL/STAT1/ABCA1 pathway). Pharmacological inhibition of AXL decreased astrocytic phagocytosis both in vivo and in vitro. Mouse CCI TBI model, pharmacological inhibition (R428), siRNA transfection, Western blot, flow cytometry, RT-PCR Journal of neuroinflammation Medium 34233703
2023 LZTR1 acts as a substrate-specific adaptor of CUL3-dependent ubiquitin ligase that targets AXL (and EGFR) for ubiquitin-dependent lysosomal degradation. Pathogenic LZTR1 cancer mutations fail to promote AXL degradation, resulting in AXL accumulation and dysregulated growth factor signaling. LZTR1-mutant tumors accumulate AXL and show specific vulnerability to AXL inhibition. Unbiased biochemical screens, Co-IP, genetic loss-of-function (conditional Lztr1 mouse KO), ubiquitination assays, mouse tumor models Cancer discovery High 36445254
2020 p85β (PIK3R2) upregulates AXL protein levels by disrupting its autophagic degradation. Mechanistically, p85β alters phosphorylation of TRIM2 (an E3 ligase) and optineurin (an autophagy receptor), which mediate selective autophagic degradation of AXL. This AXL upregulation by p85β activates AKT-independent PDK1/SGK3 signaling. Co-immunoprecipitation, phosphorylation assays, autophagy inhibition, siRNA knockdown, overexpression studies Nature communications High 32385243
2024 STAMBPL1 elevates AXL protein abundance and surface accumulation by diminishing TRIM21-mediated K63-linked ubiquitination and subsequent lysosomal degradation of AXL. This stabilization of AXL enhances mesenchymal gene expression while suppressing CXCL9/10 and HLA expression in kidney clear cell carcinoma. Co-immunoprecipitation, ubiquitination assays (K63 linkage-specific), protein stability assays, STAMBPL1 knockdown/overexpression Advanced science Medium 39527690
2023 NAT10 promotes mRNA stability of AXL in an N4-acetylcytidine (ac4C)-dependent manner, leading to increased AXL expression and promoting pancreatic ductal adenocarcinoma cell proliferation and metastasis. ac4C modification assays, mRNA stability assays, NAT10 knockdown/overexpression, in vitro and in vivo tumor models Experimental cell research Medium 37156457
2020 Phosphatidylethanolamine (PE) synergizes with phosphatidylserine (PS) to enhance Gas6 binding and AXL-mediated efferocytosis and virus entry. Liposomes containing both PE and PS bound Gas6 and were engulfed by AXL-expressing cells much more efficiently than PS alone, demonstrating that PE co-recognition maximizes PS receptor (AXL)-mediated processes. Liposome binding assays, Gas6 binding quantification, AXL-expressing cell efferocytosis assays, pseudovirus and live virus infection assays Journal of virology Medium 33115868
2019 AXL, but not MERTK or TYRO3, shows a dual regulatory function in invadopodia formation in melanoma cells: both depletion and overexpression of AXL enhanced invadopodia formation. AXL depletion upregulates ERBB3 signaling, which activates core invadopodia regulators. High AXL expression is inversely correlated with ERBB3 expression across melanoma cell lines. siRNA screen (microscopy-based), knockdown and overexpression, invadopodia formation and activity assays, bioinformatic analysis of cell line expression data Cancer research Medium 30914429
2018 Axl and Tyro3, but not Mertk, are required for platelet activation and thrombus formation. Loss of Axl in platelets reduced aggregation, spreading, integrin activation (JON/A binding), and P-selectin expression, and decreased tyrosine phosphorylation of Syk and PLCγ2 upon GPVI agonist stimulation. Anti-Axl neutralizing antibody or recombinant Axl extracellular domain (but not Gas6-neutralizing antibody) inhibited platelet aggregation, indicating ligand-independent or non-Gas6 mechanisms. Single TAM receptor knockout mice, in vitro platelet aggregation/activation assays, flow cytometry, Western blot for Syk/PLCγ2 phosphorylation, neutralizing antibodies, in vivo laser-induced thrombosis model Cell communication and signaling Medium 30541554
2019 AP-1 transcription factors c-JUN and c-FOS regulate AXL overexpression in HNSCC and ESCC. Silencing c-JUN or c-FOS downregulated AXL expression. JNK inhibition (SP600125) reduced AXL expression, and combined JNK + PI3K inhibition had synergistic anti-proliferative effects, establishing the JNK→AP-1→AXL transcriptional axis as a mechanism of AXL upregulation driving therapy resistance. siRNA silencing (c-JUN, c-FOS), qRT-PCR, Western blot, pharmacological inhibitors, in vitro proliferation assays, cell line-derived and patient-derived xenograft models JCI insight Medium 30860495
2018 AXL mediates cell invasion in esophageal adenocarcinoma through regulation of lysosome peripheral distribution and cathepsin B secretion. AXL-dependent peripheral lysosome distribution and invasion are mediated by extracellular acidification, which is potentiated by AXL-induced lactate secretion through AKT-NF-κB-dependent MCT-1 regulation. AXL knockdown, lysosome trafficking assays, cathepsin B secretion measurement, extracellular pH measurement, AKT/NF-κB pathway analysis, AXL inhibitor R428 Neoplasia Medium 30189359
2020 AXL regulates apolipoprotein E (apoE) homeostasis in human astrocytes. AXL-deficient astrocytoma cells show significantly attenuated apoE expression and secretion; reconstitution with either wild-type Axl or kinase-dead Axl significantly restored apoE baseline levels, demonstrating that Axl maintains apoE homeostasis independent of its kinase activity. AXL inhibition also upregulates ABCA1 expression. AXL-/- cell line generation, cDNA reconstitution (wild-type and kinase-dead Axl), high-throughput phenotypic screen, ELISA (apoE secretion), Western blot Molecular brain Medium 32366277
2020 AXL suppresses TP53 transcription by binding to the initial 600 bp sequence at the 5' end of the TP53 promoter, as demonstrated by chromatin immunoprecipitation-qPCR and sequencing. AXL knockdown induced wild-type and mutant p53 expression, and the anti-proliferative and anti-migratory effects of AXL silencing were attenuated by TP53 knockdown, establishing a feedback regulatory loop between AXL and p53. AXL shRNA knockdown, chromatin immunoprecipitation (ChIP)-qPCR, TP53 promoter dual luciferase assay, immunofluorescence, qRT-PCR Cancers Medium 32992696
2023 AXL facilitates African swine fever virus (ASFV) entry into porcine alveolar macrophages via macropinocytosis by acting as a phosphatidylserine (PS) receptor; ASFV displays PS on its envelope as viral apoptotic mimicry to engage AXL. AXL was identified as the most important PS receptor by RNA interference screening; AXL knockout decreased ASFV internalization and replication, and deletion of the intracellular kinase domain or AXL inhibitor R428 significantly inhibited ASFV internalization. RNA interference screening, AXL gene knockout (MA104 cells), neutralizing antibody against AXL extracellular domain, kinase domain deletion mutant, AXL inhibitor R428, macropinocytosis assays Journal of virology Medium 37382521
2023 AXL inhibits M2 macrophage polarization; a specific anti-AXL antibody blocked bone marrow-derived macrophage M2-polarization in vitro, and targeting AXL in M2-macrophages suppressed CSF-1 production and eliminated M2-macrophages in the tumor microenvironment. Anti-AXL antibody treatment, BMDM polarization assays, CSF-1 measurement, in vivo tumor models with flow cytometry analysis of immune infiltrates Acta pharmacologica Sinica Low 36650292
2022 AXL, CDCP1, and SRC form a signaling axis conferring acquired osimertinib resistance in NSCLC. Silencing CDCP1 or AXL restored sensitivity to osimertinib with reduced SRC and AKT activation; dual silencing of both CDCP1 and AXL further increased sensitivity, establishing AXL/SFK/AKT as a bypass signaling pathway. siRNA knockdown (AXL, CDCP1, SRC), Western blot for pathway activation, pharmacological inhibition (dasatinib), osimertinib-resistant cell line development Scientific reports Medium 35643725
2023 Axl promotes M1 macrophage polarization via the STAT1/HIF-1α signaling pathway in intracranial aneurysm. R428 (AXL inhibitor) inhibited phosphorylation of Axl and STAT1 and expression of HIF-1α, IL-1β, NOS2, and MMP9 in LPS/IFN-γ-stimulated macrophages. STAT1 knockdown abolished Axl-mediated M1 macrophage polarization. Mouse IA model, bone marrow-derived macrophage stimulation, AXL inhibitor R428, rmGas6 treatment, STAT1 siRNA knockdown, Western blot, immunohistochemistry Frontiers in immunology Medium 37223093
2020 Pericyte FAK negatively regulates Gas6-stimulated phosphorylation of Axl; loss of pericyte FAK enhances Gas6-stimulated Axl phosphorylation with upregulation of Cyr61, driving enhanced tumour growth. Pericyte-derived Cyr61 then instructs tumour cells to elevate expression of pro-angiogenic Tissue Factor. Pericyte-specific FAK knockout mouse models (multiple cancer models), phosphorylation assays, immunohistochemistry, multiple tumor models (melanoma, lung carcinoma, insulinoma) Nature communications Medium 32499572
2018 BRAF and AXL are oncogenic drivers of RIPK3 expression loss in cancer, thereby suppressing necroptosis sensitivity. Inhibition of AXL (or BRAF) can rescue RIPK3 expression loss and restore necroptosis sensitivity in cancer cell lines. Genome-wide bioinformatics analysis of 941 cancer cell lines, necroptosis sensitivity screen, AXL/BRAF inhibitor treatment with RIPK3 expression rescue assays PLoS biology Low 30157175
1992 The murine Ufo/Axl receptor encodes a novel tyrosine kinase receptor with an extracellular domain containing two immunoglobulin-like and two fibronectin type III repeats (87.6% amino acid identity with human). RNA in situ hybridization showed onset of specific ufo expression in late embryogenesis (day 12.5 post coitum), localized to subepidermal cells, mesenchymal cells, organ capsules, and connective tissue structures of mesodermal origin. Molecular cloning, amino acid sequence comparison, chromosomal mapping, RNA in situ hybridization Oncogene Medium 1320243

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 Giving AXL the axe: targeting AXL in human malignancy. British journal of cancer 272 28072762
2005 Structural basis for Gas6-Axl signalling. The EMBO journal 238 16362042
2005 Expression of axl in lung adenocarcinoma and correlation with tumor progression. Neoplasia (New York, N.Y.) 226 16354588
2006 Signalling and functional diversity within the Axl subfamily of receptor tyrosine kinases. Cytokine & growth factor reviews 217 16737840
2011 Targeting Axl and Mer kinases in cancer. Molecular cancer therapeutics 190 21933973
2015 AXL Inhibitors in Cancer: A Medicinal Chemistry Perspective. Journal of medicinal chemistry 168 26555154
2014 AXL mediates resistance to cetuximab therapy. Cancer research 167 25136066
2014 AXL kinase as a novel target for cancer therapy. Oncotarget 157 25337673
2014 Axl as a mediator of cellular growth and survival. Oncotarget 157 25344858
1997 Intracellular signaling of the Ufo/Axl receptor tyrosine kinase is mediated mainly by a multi-substrate docking-site. Oncogene 148 9178760
2017 AXL-Driven EMT State as a Targetable Conduit in Cancer. Cancer research 140 28667075
2012 Axl-dependent signalling: a clinical update. Clinical science (London, England : 1979) 134 22187964
2016 The Receptor Tyrosine Kinase AXL in Cancer Progression. Cancers 132 27834845
2010 The Tyro3 receptor kinase Axl enhances macropinocytosis of Zaire ebolavirus. Journal of virology 132 21047970
2018 Activation of the Receptor Tyrosine Kinase AXL Regulates the Immune Microenvironment in Glioblastoma. Cancer research 127 29531161
2014 An engineered Axl 'decoy receptor' effectively silences the Gas6-Axl signaling axis. Nature chemical biology 124 25242553
2020 Gas6/Axl Signaling Pathway in the Tumor Immune Microenvironment. Cancers 114 32660000
2016 Molecular Pathways: AXL, a Membrane Receptor Mediator of Resistance to Therapy. Clinical cancer research : an official journal of the American Association for Cancer Research 100 26763248
2006 Axl, a receptor tyrosine kinase, mediates flow-induced vascular remodeling. Circulation research 98 16627783
2016 Inhibition of the GAS6/AXL pathway augments the efficacy of chemotherapies. The Journal of clinical investigation 94 27893463
2003 Receptor tyrosine kinase Axl modulates the osteogenic differentiation of pericytes. Circulation research 84 12730092
2023 AXL in cancer: a modulator of drug resistance and therapeutic target. Journal of experimental & clinical cancer research : CR 83 37328828
2021 Macrophage AXL receptor tyrosine kinase inflames the heart after reperfused myocardial infarction. The Journal of clinical investigation 82 33529176
2018 Cabozantinib: Multi-kinase Inhibitor of MET, AXL, RET, and VEGFR2. Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer 82 30069760
2018 BRAF and AXL oncogenes drive RIPK3 expression loss in cancer. PLoS biology 74 30157175
2004 Expression of the receptor tyrosine kinase Axl promotes ocular melanoma cell survival. Cancer research 74 14729616
2019 Axl kinase drives immune checkpoint and chemokine signalling pathways in lung adenocarcinomas. Molecular cancer 72 30744655
2014 Axl kinase as a key target for oncology: focus on small molecule inhibitors. Molecular cancer therapeutics 69 25139999
1992 The murine ufo receptor: molecular cloning, chromosomal localization and in situ expression analysis. Oncogene 68 1320243
2021 Therapeutic Targeting of the Gas6/Axl Signaling Pathway in Cancer. International journal of molecular sciences 64 34576116
2018 Axl inhibitors as novel cancer therapeutic agents. Life sciences 60 29496493
2025 AXL signaling in cancer: from molecular insights to targeted therapies. Signal transduction and targeted therapy 58 39924521
1999 Expression of the Axl receptor tyrosine kinase in human thyroid carcinoma. Thyroid : official journal of the American Thyroid Association 58 10411118
1999 Axl-gas6 interaction counteracts E1A-mediated cell growth suppression and proapoptotic activity. Molecular and cellular biology 56 10567533
2020 AXL as a Target in Breast Cancer Therapy. Journal of oncology 55 32148495
2020 AXL confers cell migration and invasion by hijacking a PEAK1-regulated focal adhesion protein network. Nature communications 55 32681075
2003 Expression of the proto-oncogene Axl in renal cell carcinoma. DNA and cell biology 55 14565870
2020 Pericyte FAK negatively regulates Gas6/Axl signalling to suppress tumour angiogenesis and tumour growth. Nature communications 54 32499572
2019 Repression of AXL expression by AP-1/JNK blockage overcomes resistance to PI3Ka therapy. JCI insight 54 30860495
2014 Axl receptor tyrosine kinase expression in breast cancer. Journal of clinical pathology 52 24904064
2022 The Development of AXL Inhibitors in Lung Cancer: Recent Progress and Challenges. Frontiers in oncology 48 35311091
2018 Engineering Axl specific CAR and SynNotch receptor for cancer therapy. Scientific reports 48 29497107
2018 MERTK Mediates Intrinsic and Adaptive Resistance to AXL-targeting Agents. Molecular cancer therapeutics 47 30093568
2018 AXL Is a Putative Tumor Suppressor and Dormancy Regulator in Prostate Cancer. Molecular cancer research : MCR 45 30291220
2014 AXL receptor tyrosine kinase is increased in patients with heart failure. International journal of cardiology 45 24681018
2023 AXL Inhibitors: Status of Clinical Development. Current oncology reports 42 36920638
2022 Gas6 Promotes Microglia Efferocytosis and Suppresses Inflammation Through Activating Axl/Rac1 Signaling in Subarachnoid Hemorrhage Mice. Translational stroke research 42 36324028
2021 AXL Receptor in Cancer Metastasis and Drug Resistance: When Normal Functions Go Askew. Cancers 41 34638349
2007 S-Nitrosylation and uncompetitive/fast off-rate (UFO) drug therapy in neurodegenerative disorders of protein misfolding. Cell death and differentiation 41 17431424
2022 AXL inhibition improves BRAF-targeted treatment in melanoma. Scientific reports 40 35332208
2020 Soluble AXL as a marker of disease progression and survival in melanoma. PloS one 40 31917795
2015 AXL receptor tyrosine kinase as a therapeutic target in NSCLC. Lung Cancer (Auckland, N.Z.) 40 28210148
2023 The F-box protein UFO controls flower development by redirecting the master transcription factor LEAFY to new cis-elements. Nature plants 39 36732360
2023 NAT10-mediated AXL mRNA N4-acetylcytidine modification promotes pancreatic carcinoma progression. Experimental cell research 39 37156457
2021 AXL Is a Potential Target for the Treatment of Intestinal Fibrosis. Inflammatory bowel diseases 39 32676663
2021 AXL kinase-mediated astrocytic phagocytosis modulates outcomes of traumatic brain injury. Journal of neuroinflammation 39 34233703
2017 The receptor tyrosine kinase AXL promotes migration and invasion in colorectal cancer. PloS one 39 28727830
2016 Role of the Receptor Tyrosine Kinase Axl and its Targeting in Cancer Cells. Current medicinal chemistry 39 27048336
2021 Immune Evasion Mechanism and AXL. Frontiers in oncology 38 34778071
2019 Cross-Talk between Receptor Tyrosine Kinases AXL and ERBB3 Regulates Invadopodia Formation in Melanoma Cells. Cancer research 37 30914429
2016 Axl Receptor Axis: A New Therapeutic Target in Lung Cancer. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 37 27130831
1996 Differential expression of the ufo/axl oncogene in human leukemia-lymphoma cell lines. Leukemia 37 8656672
2020 Therapeutic aspects of the Axl/Gas6 molecular system. Drug discovery today 36 33002607
2023 Gas6/AXL pathway: immunological landscape and therapeutic potential. Frontiers in oncology 35 37265798
2017 Protein S drives oral squamous cell carcinoma tumorigenicity through regulation of AXL. Oncotarget 35 28118606
2017 Expression and role of TYRO3 and AXL as potential therapeutical targets in leiomyosarcoma. British journal of cancer 35 29024938
2016 Impact of Expression of Vimentin and Axl in Breast Cancer. Clinical breast cancer 35 27506606
2019 Expression of AXL receptor tyrosine kinase relates to monocyte dysfunction and severity of cirrhosis. Life science alliance 34 31822557
2020 Phosphatidylethanolamine and Phosphatidylserine Synergize To Enhance GAS6/AXL-Mediated Virus Infection and Efferocytosis. Journal of virology 32 33115868
2016 Gene of the month: Axl. Journal of clinical pathology 31 26951083
1997 Recent progress on the role of Axl, a receptor tyrosine kinase, in malignant transformation of myeloid leukemias. Leukemia & lymphoma 31 9130617
2022 AXL and MET in Hepatocellular Carcinoma: A Systematic Literature Review. Liver cancer 29 35634427
2021 AXL Is a Key Factor for Cell Plasticity and Promotes Metastasis in Pancreatic Cancer. Molecular cancer research : MCR 29 33811159
2021 AXL Inhibitor TP-0903 Reduces Metastasis and Therapy Resistance in Pancreatic Cancer. Molecular cancer therapeutics 28 34675118
2020 p85β regulates autophagic degradation of AXL to activate oncogenic signaling. Nature communications 27 32385243
2020 AXL Receptor in Breast Cancer: Molecular Involvement and Therapeutic Limitations. International journal of molecular sciences 27 33182542
2018 Dynamics of Axl Receptor Shedding in Hepatocellular Carcinoma and Its Implication for Theranostics. International journal of molecular sciences 27 30567378
2018 Does Axl have potential as a therapeutic target in pancreatic cancer? Expert opinion on therapeutic targets 26 30244621
2017 LncRNA-MALAT1-mediated Axl promotes cell invasion and migration in human neuroblastoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 26 28468579
2018 AXL Mediates Esophageal Adenocarcinoma Cell Invasion through Regulation of Extracellular Acidification and Lysosome Trafficking. Neoplasia (New York, N.Y.) 24 30189359
2021 Targeting AXL in NSCLC. Lung Cancer (Auckland, N.Z.) 23 34408519
2020 Axl-148b chimeric aptamers inhibit breast cancer and melanoma progression. International journal of biological sciences 23 32174798
2023 AXL antibody and AXL-ADC mediate antitumor efficacy via targeting AXL in tumor-intrinsic epithelial-mesenchymal transition and tumor-associated M2-like macrophage. Acta pharmacologica Sinica 22 36650292
2022 AXL/CDCP1/SRC axis confers acquired resistance to osimertinib in lung cancer. Scientific reports 22 35643725
2019 AXL targeting reduces fibrosis development in experimental unilateral ureteral obstruction. Physiological reports 22 31134766
2018 Tyro3, Axl, and Mertk receptors differentially participate in platelet activation and thrombus formation. Cell communication and signaling : CCS 22 30541554
2023 Role of miR-944/MMP10/AXL- axis in lymph node metastasis in tongue cancer. Communications biology 20 36650344
2023 Coreceptor AXL Facilitates African Swine Fever Virus Entry via Apoptotic Mimicry. Journal of virology 20 37382521
2020 MicroRNA 34a-AXL Axis Regulates Vasculogenic Mimicry Formation in Breast Cancer Cells. Genes 20 33374832
2019 Mechanism of gut microbiota and Axl/SOCS3 in experimental autoimmune encephalomyelitis. Bioscience reports 20 31221818
2017 Epigenetic regulation of AXL and risk of childhood asthma symptoms. Clinical epigenetics 20 29177020
2016 Role of AXL expression in non-small cell lung cancer. Oncology letters 20 28105215
2023 Axl promotes intracranial aneurysm rupture by regulating macrophage polarization toward M1 via STAT1/HIF-1α. Frontiers in immunology 19 37223093
2021 Targeting the AXL Receptor in Combating Smoking-related Pulmonary Fibrosis. American journal of respiratory cell and molecular biology 19 33730527
2019 Unknown fates of (brain) oxidation or UFO: Close encounters with neuronal senescence. Free radical biology & medicine 19 30639615
2024 STAMBPL1/TRIM21 Balances AXL Stability Impacting Mesenchymal Phenotype and Immune Response in KIRC. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 18 39527690
2023 LZTR1 Mutation Mediates Oncogenesis through Stabilization of EGFR and AXL. Cancer discovery 18 36445254
2021 AXL, an Important Host Factor for DENV and ZIKV Replication. Frontiers in cellular and infection microbiology 18 33954117
2020 Axl receptor tyrosine kinase is a regulator of apolipoprotein E. Molecular brain 17 32366277
2020 AXL Inactivation Inhibits Mesothelioma Growth and Migration via Regulation of p53 Expression. Cancers 17 32992696

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