ArticleScience signaling2017
RETRACTED: The receptor tyrosine kinase AXL mediates nuclear translocation of the epidermal growth factor receptor.
Article in Science signaling, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 27 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 46 citations in OpenAlex.
- Molecular Insights into HPV-Driven Cervical Cancer: Oncoproteins, Immune Evasion, and Epigenetic Modifications.Microorganisms · 2025Review
- The effect of inhibition of receptor tyrosine kinase AXL on DNA damage response in ovarian cancer.Communications biology · 2023Article
- AXL upregulates c‑Myc expression through AKT and ERK signaling pathways in breast cancers.Molecular and clinical oncology · 2023Article
- Programmed death ligand 1 signals in cancer cells.Nature reviews. Cancer · 2022Review
- Review
- Nuclear moonlighting of the secreted growth factor heregulin drives endocrine-resistant breast cancer independently of HER2/HER3 signaling.American journal of cancer research · 2022Article
- Primaquine Inhibits the Endosomal Trafficking and Nuclear Localization of EGFR and Induces the Apoptosis of Breast Cancer Cells by Nuclear EGFR/Stat3-Mediated c-Myc Downregulation.International journal of molecular sciences · 2021Article
- Retraction.Science signaling · 2021Article
- AXL Receptor in Cancer Metastasis and Drug Resistance: When Normal Functions Go Askew.Cancers · 2021Review
- Host-Dependent Phenotypic Resistance to EGFR Tyrosine Kinase Inhibitors.Cancer research · 2021Article
- Upfront admixing antibodies and EGFR inhibitors preempts sequential treatments in lung cancer models.EMBO molecular medicine · 2021Article
- Evidence for 2-Methoxyestradiol-Mediated Inhibition of Receptor Tyrosine Kinase RON in the Management of Prostate Cancer.International journal of molecular sciences · 2021Article
- Article
- 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
- Review
- Frontiers of ctDNA, targeted therapies, and immunotherapy in non-small-cell lung cancer.Translational lung cancer research · 2020Review
- Diverse roles of epidermal growth factors receptors in oral and cutaneous canine melanomas.BMC veterinary research · 2020Article
- Nuclear IGF1R interact with PCNA to preserve DNA replication after DNA-damage in a variety of human cancers.PloS one · 2020Article
- AXL as a Target in Breast Cancer Therapy.Journal of oncology · 2020Review
- Molecular Signatures for Combined Targeted Treatments in Diffuse Malignant Peritoneal Mesothelioma.International journal of molecular sciences · 2019Article
Corrections and comments
- Retraction · 2021-11-09Duplication of/in Image · Error in Image · Investigation by Company/Institution · Original Data and/or Images not Provided and/or not Available · · see also: https://pubpeer.com/publications/51FBF301F19C689D548558937B326C;
- Commented on by
- RetractedRetraction.2021
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
The epidermal growth factor receptor (EGFR) is a therapeutic target in patients with various cancers. Unfortunately, resistance to EGFR-targeted therapeutics is common. Previous studies identified two mechanisms of resistance to the EGFR monoclonal antibody cetuximab. Nuclear translocation of EGFR bypasses the inhibitory effects of cetuximab, and the receptor tyrosine kinase AXL mediates cetuximab resistance by maintaining EGFR activation and downstream signaling. Thus, we hypothesized that AXL mediated the nuclear translocation of EGFR in the setting of cetuximab resistance. Cetuximab-resistant clones of non-small cell lung cancer in culture and patient-derived xenografts in mice had increased abundance of AXL and nuclear EGFR (nEGFR). Cellular fractionation analysis, super-resolution microscopy, and electron microscopy revealed that genetic loss of AXL reduced the accumulation of nEGFR. SRC family kinases (SFKs) and HER family ligands promote the nuclear translocation of EGFR. We found that AXL knockdown reduced the expression of the genes encoding the SFK family members YES and LYN and the ligand neuregulin-1 (NRG1). AXL knockdown also decreased the interaction between EGFR and the related receptor HER3 and accumulation of HER3 in the nucleus. Overexpression of LYN and NRG1 in cells depleted of AXL resulted in accumulation of nEGFR, rescuing the deficit induced by lack of AXL. Collectively, these data uncover a previously unrecognized role for AXL in regulating the nuclear translocation of EGFR and suggest that AXL-mediated SFK and NRG1 expression promote this process.
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What OpenQuestion holds
Registered trials
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.