ArticlePloS one2014
Glycogen synthase kinase 3 protein kinase activity is frequently elevated in human non-small cell lung carcinoma and supports tumour cell proliferation.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 28 citations in OpenAlex.
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- Concurrent targeting of GSK3 and MEK as a therapeutic strategy to treat pancreatic ductal adenocarcinoma.Cancer science · 2024Article
- Biphasic function of GSK3β in gefitinib‑resistant NSCLC with or without EGFR mutations.Experimental and therapeutic medicine · 2023Article
- Selection of Optimal Cell Lines for High-Content Phenotypic Screening.ACS chemical biology · 2023Article
- Selection of optimal cell lines for high-content phenotypic screening.bioRxiv : the preprint server for biology · 2023Article
- Review
- Cascaded Wx: A Novel Prognosis-Related Feature Selection Framework in Human Lung Adenocarcinoma Transcriptomes.Frontiers in genetics · 2019Article
- Tumor growth suppression using a combination of taxol-based therapy and GSK3 inhibition in non-small cell lung cancer.PloS one · 2019Article
- Aberrant expression of glycogen synthase kinase-3β in human breast and head and neck cancer.Oncology letters · 2018Article
- Hirsutine induces mPTP-dependent apoptosis through ROCK1/PTEN/PI3K/GSK3β pathway in human lung cancer cells.Cell death & disease · 2018Article
- In Vitro and In Vivo Antitumor and Anti-Inflammatory Capabilities of the Novel GSK3 and CDK9 Inhibitor ABC1183.The Journal of pharmacology and experimental therapeutics · 2018Article
- Antagonistic role of GSK3 isoforms in glioma survival.Journal of Cancer · 2018Article
- DRP5 is involved in cancer cell growth and predicts poor prognosis in human osteosarcoma.Cancer medicine · 2017Article
- Molecular Pathways: Revisiting Glycogen Synthase Kinase-3β as a Target for the Treatment of Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Review
- Glycogen synthase kinase-3β is a pivotal mediator of cancer invasion and resistance to therapy.Cancer science · 2016Review
- Article
- Glycogen synthase kinase-3: a potential preventive target for prostate cancer management.Urologic oncology · 2015Review
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundGlycogen synthase kinase 3 (GSK3) is a central regulator of cellular metabolism, development and growth. GSK3 activity was thought to oppose tumourigenesis, yet recent studies indicate that it may support tumour growth in some cancer types including in non-small cell lung carcinoma (NSCLC). We examined the undefined role of GSK3 protein kinase activity in tissue from human NSCLC.
methodsThe expression and protein kinase activity of GSK3 was determined in 29 fresh frozen samples of human NSCLC and patient-matched normal lung tissue by quantitative immunoassay and western blotting for the phosphorylation of three distinct GSK3 substrates in situ (glycogen synthase, RelA and CRMP-2). The proliferation and sensitivity to the small-molecule GSK3 inhibitor; CHIR99021, of NSCLC cell lines (Hcc193, H1975, PC9 and A549) and non-neoplastic type II pneumocytes was further assessed in adherent culture.
resultsExpression and protein kinase activity of GSK3 was elevated in 41% of human NSCLC samples when compared to patient-matched control tissue. Phosphorylation of GSK3α/β at the inhibitory S21/9 residue was a poor biomarker for activity in tumour samples. The GSK3 inhibitor, CHIR99021 dose-dependently reduced the proliferation of three NSCLC cell lines yet was ineffective against type II pneumocytes.
conclusionNSCLC tumours with elevated GSK3 protein kinase activity may have evolved dependence on the kinase for sustained growth. Our results provide further important rationale for exploring the use of GSK3 inhibitors in treating NSCLC.
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