ArticleJCI insight2019
Repression of AXL expression by AP-1/JNK blockage overcomes resistance to PI3Ka therapy.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 65 citations in OpenAlex.
- CaHoT-GRN: context-aware high-order topology learning for robust single-cell gene regulatory network inference.Briefings in bioinformatics · 2026Article
- CRISPR knockout screens reveal JUN as the master mediator of resistance to MAPK inhibition in KRAS-mutant pancreatic cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- PIK75 effectively reverses PI3K‒AKT activation caused by palbociclib resistance and synergistically inhibits the progression of esophageal squamous cell carcinoma.Scientific reports · 2025Article
- From Carcinogenesis to Drug Resistance: The Multifaceted Role of Oxidative Stress in Head and Neck Cancer.Cancers · 2025Review
- Targeting rapid TKI-induced AXL upregulation overcomes adaptive ERK reactivation and exerts antileukemic effects in FLT3/ITD acute myeloid leukemia.Molecular oncology · 2025Article
- Insights into expression and localization of HPV16 LCR-associated transcription factors and association with LCR activity in HNSCC.Molecular therapy. Oncology · 2025Article
- AXL signaling in cancer: from molecular insights to targeted therapies.Signal transduction and targeted therapy · 2025Review
- CD276-dependent efferocytosis by tumor-associated macrophages promotes immune evasion in bladder cancer.Nature communications · 2024Article
- Therapeutic targeting of the functionally elusive TAM receptor family.Nature reviews. Drug discovery · 2024Review
- β1 integrin mediates unresponsiveness to PI3Kα inhibition for radiochemosensitization of 3D HNSCC models.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Article
- 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
- Activation of the EGFR/PI3K/AKT pathway limits the efficacy of trametinib treatment in head and neck cancer.Molecular oncology · 2023Article
- Breast cancer stem cells tolerate chromosomal instability during tumor progression via c-Jun/AXL stress signaling.Heliyon · 2023Article
- HPV18 E6 inhibits α-ketoglutarate-induced pyroptosis of esophageal squamous cell carcinoma cells via the P53/MDH1/ROS/GSDMC pathway.FEBS open bio · 2023Article
- Developing a dual VEGF/PDL1 inhibitor based on high-affinity scFv heterodimers as an anti-cancer therapeutic strategy.Scientific reports · 2023Article
- AXL in cancer: a modulator of drug resistance and therapeutic target.Journal of experimental & clinical cancer research : CR · 2023Review
- Mutated HRAS Activates YAP1-AXL Signaling to Drive Metastasis of Head and Neck Cancer.Cancer research · 2023Article
- Transcriptomic analysis of the effects of the HPV18 E6E7 gene on the cell death mode in esophageal squamous cell carcinoma.Oncology letters · 2023Article
- Targeted therapy for head and neck cancer: signaling pathways and clinical studies.Signal transduction and targeted therapy · 2023Review
- Axl regulated survival/proliferation network and its therapeutic intervention in mouse models of glomerulonephritis.Arthritis research & therapy · 2022Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
AXL overexpression is a common resistance mechanism to anti-cancer therapies, including the resistance to BYL719 (Alpelisib) - the p110α isoform specific inhibitor of phosphoinositide 3-kinase (PI3K) - in esophagus and head and neck squamous cell carcinoma (ESCC, HNSCC respectively). However, the mechanisms underlying AXL overexpression in resistance to BYL719 remain elusive. Here we demonstrated that the AP-1 transcription factors, c-JUN and c-FOS, regulate AXL overexpression in HNSCC and ESCC. The expression of AXL was correlated with that of c-JUN both in HNSCC patients and in HNSCC and ESCC cell lines. Silencing of c-JUN and c-FOS expression in tumor cells downregulated AXL expression and enhanced the sensitivity of human papilloma virus positive (HPVPos) and negative (HPVNeg) tumor cells to BYL719 in vitro. Blocking of the c-JUN N-terminal kinase (JNK) using SP600125 in combination with BYL719 showed a synergistic anti-proliferative effect in vitro, which was accompanied by AXL downregulation and potent inhibition of the mTOR pathway. In vivo, the BYL719-SP600125 drug combination led to the arrest of tumor growth in cell line-derived and patient-derived xenograft models, and in syngeneic head and neck murine cancer models. Collectively, our data suggests that JNK inhibition in combination with anti-PI3K therapy is a new therapeutic strategy that should be tested in HPVPos and HPVNeg HNSCC and ESCC patients.
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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 Socratic graph.