ArticleOncotarget2016
TOPK promotes lung cancer resistance to EGFR tyrosine kinase inhibitors by phosphorylating and activating c-Jun.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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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
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Who cites it
32 citing papers in PubMed, 46 citations in OpenAlex.
- Targeting the TOPK-STAT3 pathway in keratinocytes and mast cells mediates the therapeutic attenuation of Atopic dermatitis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Advances in T-Lymphokine-activated Killer Cell-originated Protein Kinase Research in Cancer Over the Past Thirty Years.Journal of cancer prevention · 2026Review
- Stratified signaling network remodeling of kinase-transcription factors' interactions in Parkinson's disease.Bioinformatics advances · 2026Article
- The Roles of TOPK in Tumorigenesis and Development: Structure, Mechanisms, Pathways, and Therapeutic Implications.International journal of biological sciences · 2026Review
- PDZ-Binding Kinase, a Novel Regulator of Vascular Remodeling in Pulmonary Arterial Hypertension.Circulation · 2024Article
- TOPK Inhibition Enhances the Sensitivity of Colorectal Cancer Cells to Radiotherapy by Reducing the DNA Damage Response.Current medical science · 2024Article
- Phosphorylation of PBK at Thr9 by CDK5 correlates with invasion of prolactinomas.CNS neuroscience & therapeutics · 2024Article
- KRASJournal of cellular and molecular medicine · 2023Article
- FYN/TOPK/HSPB1 axis facilitates the proliferation and metastasis of gastric cancer.Journal of experimental & clinical cancer research : CR · 2023Article
- Inhibiting ALK-TOPK signaling pathway promotes cell apoptosis of ALK-positive NSCLC.Cell death & disease · 2022Article
- TOPK/PBK is phosphorylated by ERK2 at serine 32, promotes tumorigenesis and is involved in sorafenib resistance in RCC.Cell death & disease · 2022Article
- The role of T-LAK cell-originated protein kinase in targeted cancer therapy.Molecular and cellular biochemistry · 2022Review
- Review
- 3-Deoxysappanchalcone Inhibits Skin Cancer Proliferation by Regulating T-Lymphokine-Activated Killer Cell-Originated Protein KinaseFrontiers in cell and developmental biology · 2021Article
- Combined Small and Squamous Transformation in EGFR-mutated Lung Adenocarcinoma.Internal medicine (Tokyo, Japan) · 2020Article
- Acetylshikonin suppressed growth of colorectal tumour tissue and cells by inhibiting the intracellular kinase, T-lymphokine-activated killer cell-originated protein kinase.British journal of pharmacology · 2020Article
- Suppression of the solar ultraviolet-induced skin carcinogenesis by TOPK inhibitor HI-TOPK-032.Oncogene · 2020Article
- Targeting the COX2/MET/TOPK signaling axis induces apoptosis in gefitinib-resistant NSCLC cells.Cell death & disease · 2019Article
- Crosstalk between the Akt/mTORC1 and NF-κB signaling pathways promotes hypoxia-induced pulmonary hypertension by increasing DPP4 expression in PASMCs.Acta pharmacologica Sinica · 2019Article
- Baicalin suppresses lung cancer growth by targeting PDZ-binding kinase/T-LAK cell-originated protein kinase.Bioscience reports · 2019Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tyrosine kinase inhibitors (TKIs) targeting the epidermal growth factor receptor (EGFR) have shown promising clinical efficacy in non-squamous non-small cell lung cancer (NSCLC); however, resistance is frequently observed in malignant cells, operating through a mechanism that remains largely unknown. The present study shows that T-lymphokine-activated killer cell-originated protein kinase (TOPK) is upregulated in NSCLC and excessively activated in TKI-refractory cells. TOPK dictates the responsiveness of lung cancers to the EGFR-targeted TKI gefitinib through the transcription factor AP-1 component c-Jun. TOPK binds directly to and phosphorylates c-Jun, which consequently activates the transcription of AP-1 target genes, including CCND1 and CDC2. TOPK silencing sensitizes EGFR-TKI-resistant lung cancer cells to gefitinib and increases gefitinib efficacy in preclinical lung adenocarcinoma xenograft models. These findings represent a novel mechanism of lung cancer resistance to TKIs and suggest that TOPK may have value both as a predictive biomarker and as a therapeutic target: TOPK-targeted therapy may synergize with EGFR-targeted therapy in lung cancers.
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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.