ArticleCellular and molecular gastroenterology and hepatology2020
LLGL1 Regulates Gemcitabine Resistance by Modulating the ERK-SP1-OSMR Pathway in Pancreatic Ductal Adenocarcinoma.
Article in Cellular and molecular gastroenterology and hepatology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 29 citations in OpenAlex.
- MMSDH facilitates ACSL4 propionylation to counteract ferroptosis upon hypoxia and impairs PDAC chemotherapy efficacy.Nature cancer · 2026Article
- Loss of LLGL1 Elevates EGFR/RAS/MAPK Signaling and Remodels EMT Markers in Huh-7 Hepatocellular Carcinoma Cells.International journal of molecular sciences · 2026Article
- Galectin-3 in tumor-stromal cells enhances gemcitabine resistance in pancreatic adenocarcinoma by suppressing oxidative phosphorylation.Genes & diseases · 2025Article
- Melatonin augments anti-tumor activity and alleviates nephrotoxicity of gemcitabine in a pancreatic cancer xenograft model targeting P62/Keap1 pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- MicroRNA-6084 orchestrates angiogenesis and liver metastasis in colorectal cancer via extracellular vesicles.JCI insight · 2025Article
- Trametinib Potentiates Anti-PD-1 Efficacy in Tumors Established from Chemotherapy-Primed Pancreatic Cancer Cells.Molecular cancer therapeutics · 2024Article
- Correlation Between Antihypertensive Drugs and Survival Among Patients with Pancreatic Ductal Adenocarcinoma.Cancers · 2024Review
- New perspectives in cancer immunotherapy: targeting IL-6 cytokine family.Journal for immunotherapy of cancer · 2023Review
- Canine interleukin-31 binds directly to OSMRβ with higher binding affinity than to IL-31RA.3 Biotech · 2023Article
- Macrophage-organoid co-culture model for identifying treatment strategies against macrophage-related gemcitabine resistance.Journal of experimental & clinical cancer research : CR · 2023Article
- Cloning, expression, purification, and immunoblotting analysis of recombinant type III fibronectin domains of human oncostatin M receptor.Molecular biology reports · 2023Article
- Combination of Tissue Microarray Profiling and Multiplexed IHC Approaches to Investigate Transport Mechanism of Nucleoside Analog Drug Resistance.Methods in molecular biology (Clifton, N.J.) · 2023Article
- The expression profile of Gasdermin C-related genes predicts the prognosis and immunotherapy response of pancreatic adenocarcinoma.American journal of cancer research · 2023Article
- Calcium channel blockers potentiate gemcitabine chemotherapy in pancreatic cancer.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Article
- circFARP1 enables cancer-associated fibroblasts to promote gemcitabine resistance in pancreatic cancer via the LIF/STAT3 axis.Molecular cancer · 2022Article
- CircRTN4 promotes pancreatic cancer progression through a novel CircRNA-miRNA-lncRNA pathway and stabilizing epithelial-mesenchymal transition protein.Molecular cancer · 2022Article
- The Regulatory Network and Role of the circRNA-miRNA-mRNA ceRNA Network in the Progression and the Immune Response of Wilms Tumor Based on RNA-Seq.Frontiers in genetics · 2022Article
- The Role of Adipokines in Pancreatic Cancer.Frontiers in oncology · 2022Review
- Case Report: Balanced Reciprocal Translocation t (17; 22) (p11.2; q11.2) and 10q23.31 Microduplication in an Infertile Male Patient Suffering From Teratozoospermia.Frontiers in genetics · 2022Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
aimsGemcitabine resistance is rapidly acquired by pancreatic ductal adenocarcinoma (PDAC) patients. Novel approaches that predict the gemcitabine response of patients and enhance gemcitabine chemosensitivity are important to improve patient survival. We aimed to identify genes as novel biomarkers to predict the gemcitabine response and the therapeutic targets to attenuate chemoresistance in PDAC cells.
methodsGenome-wide RNA interference screening was conducted to identify genes that regulated gemcitabine chemoresistance. A cell proliferation assay and a tumor formation assay were conducted to study the role of lethal giant larvae homolog 1 (LLGL1) in gemcitabine chemoresistance. Levels of LLGL1 and its regulating targets were measured by immunohistochemical staining in tumor tissues obtained from patients who received gemcitabine as a single therapeutic agent. A gene-expression microarray was conducted to identify the targets regulated by LLGL1.
resultsSilencing of LLGL1 markedly reduced the gemcitabine chemosensitivity in PDAC cells. Patients had significantly shorter survival (6 months) if they bore tumors expressing low LLGL1 level than tumors with high LLGL1 level (20 months) (hazard ratio, 0.1567; 95% CI, 0.05966-0.4117). Loss of LLGL1 promoted cytokine receptor oncostatin M receptor (OSMR) expression in PDAC cells that led to gemcitabine resistance, while knockdown of OSMR effectively rescued the chemoresistance phenotype. The LLGL1-OSMR regulatory pathway showed great clinical importance because low LLGL1 and high OSMR expressions were observed frequently in PDAC tissues. Silencing of LLGL1 induced phosphorylation of extracellular signal-regulated kinase 2 and specificity protein 1 (Sp1), promoted Sp1 (pThr453) binding at the OSMR promoter, and enhanced OSMR transcription.
conclusionsLLGL1 possessed a tumor-suppressor role as an inhibitor of chemoresistance by regulating OSMR-extracellular signal-regulated kinase 2/Sp1 signaling. The data sets generated and analyzed during the current study are available in the Gene Expression Omnibus repository (ID: GSE64681).
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