ArticlePloS one2013
Aberrant glycogen synthase kinase 3β is involved in pancreatic cancer cell invasion and resistance to therapy.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- Manzamine A: A promising marine-derived cancer therapeutic for multi-targeted interactions with E2F8, SIX1, AR, GSK-3β, and V-ATPase - A systematic review.European journal of pharmacology · 2025Pooled it
- Apoptosis, Cell Growth, and Glycogen Synthase Kinase 3β Phosphorylation in Caffeic Acid-Treated Human Malignant Melanoma Cells.Biomedicines · 2025Article
- Targeting stromal components in pancreatic ductal adenocarcinoma: a review.Ecancermedicalscience · 2025Review
- Osthole inhibits GSK-3β/AMPK/mTOR pathway-controlled glycolysis and increases radiosensitivity of subcutaneous transplanted hepatocellular carcinoma in nude mice.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2024Article
- Glycogen synthase kinase 3β: the nexus of chemoresistance, invasive capacity, and cancer stemness in pancreatic cancer.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- Alkannin Induces G2/M-Phase Arrest, Apoptosis, and Inhibition of Invasion by Targeting GSK3β in Esophageal Squamous Cell Carcinoma.Drug design, development and therapy · 2024Article
- The many faceted role of glycogen synthase kinase-3 (GSK-3) in T cells and cancer immunotherapy.Journal of cancer biology · 2024Article
- Article
- Loss of PRDX6 Aborts Proliferative and Migratory Signaling in Hepatocarcinoma Cell Lines.Antioxidants (Basel, Switzerland) · 2023Article
- The Cell Biology of Metastatic Invasion in Pancreatic Cancer: Updates and Mechanistic Insights.Cancers · 2023Review
- Glycogen Synthase Kinase 3β: A True Foe in Pancreatic Cancer.International journal of molecular sciences · 2022Review
- Decrypting a path based approach for identifying the interplay between PI3K and GSK3 signaling cascade from the perspective of cancer.Genes & diseases · 2022Review
- Nordentatin Inhibits Neuroblastoma Cell Proliferation and Migration through Regulation of GSK-3 Pathway.Current issues in molecular biology · 2022Article
- Review
- GSK-3β in Pancreatic Cancer: Spotlight on 9-ING-41, Its Therapeutic Potential and Immune Modulatory Properties.Biology · 2021Review
- Identifying Novel Actionable Targets in Colon Cancer.Biomedicines · 2021Review
- Glycogen synthase kinase 3β inhibition synergizes with PARP inhibitors through the induction of homologous recombination deficiency in colorectal cancer.Cell death & disease · 2021Article
- The role of glycogen synthase kinase 3 (GSK3) in cancer with emphasis on ovarian cancer development and progression: A comprehensive review.Bosnian journal of basic medical sciences · 2021Review
- Biological Adaptations of Tumor Cells to Radiation Therapy.Frontiers in oncology · 2021Review
- GSK-3 Inhibition Modulates Metalloproteases in a Model of Lung Inflammation and Fibrosis.Frontiers in molecular biosciences · 2021Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeThe major obstacles to treatment of pancreatic cancer are the highly invasive capacity and resistance to chemo- and radiotherapy. Glycogen synthase kinase 3β (GSK3β) regulates multiple cellular pathways and is implicated in various diseases including cancer. Here we investigate a pathological role for GSK3β in the invasive and treatment resistant phenotype of pancreatic cancer.
methodsPancreatic cancer cells were examined for GSK3β expression, phosphorylation and activity using Western blotting and in vitro kinase assay. The effects of GSK3β inhibition on cancer cell survival, proliferation, invasive ability and susceptibility to gemcitabine and radiation were examined following treatment with a pharmacological inhibitor or by RNA interference. Effects of GSK3β inhibition on cancer cell xenografts were also examined.
resultsPancreatic cancer cells showed higher expression and activity of GSK3β than non-neoplastic cells, which were associated with changes in its differential phosphorylation. Inhibition of GSK3β significantly reduced the proliferation and survival of cancer cells, sensitized them to gemcitabine and ionizing radiation, and attenuated their migration and invasion. These effects were associated with decreases in cyclin D1 expression and Rb phosphorylation. Inhibition of GSK3β also altered the subcellular localization of Rac1 and F-actin and the cellular microarchitecture, including lamellipodia. Coincident with these changes were the reduced secretion of matrix metalloproteinase-2 (MMP-2) and decreased phosphorylation of focal adhesion kinase (FAK). The effects of GSK3β inhibition on tumor invasion, susceptibility to gemcitabine, MMP-2 expression and FAK phosphorylation were observed in tumor xenografts.
conclusionThe targeting of GSK3β represents an effective strategy to overcome the dual challenges of invasiveness and treatment resistance in pancreatic cancer.
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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.