ArticleCell death & disease2022
Gemcitabine resistance of pancreatic cancer cells is mediated by IGF1R dependent upregulation of CD44 expression and isoform switching.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 47 citations in OpenAlex.
- EGR1 regulates IGF-1-stimulated pancreatic cancer cell invasion by increasing IL-11 expression.Oncology letters · 2026Article
- Protease inhibition: breaking the barriers of chemoresistance in cancer.Molecular biology reports · 2026Review
- Multifaceted roles of CD44 in cancer progression and targeted therapeutic strategies.Experimental & molecular medicine · 2026Review
- Pancreatic ductal adenocarcinoma: integrating molecular insights for targeted interventions.Signal transduction and targeted therapy · 2026Review
- SNHG10 promotes tumorigenesis through the EGFR/AKT/ERK/mTOR and miR-150-5p/VEGF-A axis, along with gemcitabine resistance in pancreatic ductal adenocarcinoma.Cell death discovery · 2026Article
- Unlocking the Power of CXCR2 Inhibition to Overcome Gemcitabine Resistance in Pancreatic Cancer.FASEB bioAdvances · 2026Article
- SLC6A14-mediated glutamine promotes SYTL4-CXCL8 axis activation to drive gemcitabine resistance and immune evasion in pancreatic cancer.Experimental & molecular medicine · 2025Article
- Proteomic Characterization of Primary Human Pancreatic Cancer Cell Lines Following Long-Term Exposure to Gemcitabine.Proteomes · 2025Article
- CD44 as a Central Integrator of Inflammation and Fibrosis: From Molecular Signaling to Environmental Modulation.International journal of molecular sciences · 2025Review
- Interfacial Stress Regulates Plasticity and Drug Resistance at the Breast Cancer-Host Interface.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Inhibiting the TGF-β1 Pathway Reduces the Aggressiveness of Intrahepatic CCA HuCCT1 CD90-Positive Cells.International journal of molecular sciences · 2025Article
- CD44 Variant Expression in Follicular Cell-Derived Thyroid Cancers: Implications for Overcoming Multidrug Resistance.Molecules (Basel, Switzerland) · 2025Review
- SLC5A3 depletion promotes apoptosis by inducing mitochondrial dysfunction and mitophagy in gemcitabine-resistant pancreatic cancer cells.Cell death & disease · 2025Article
- Clinical application and drug resistance mechanism of gemcitabine.Frontiers in cell and developmental biology · 2025Review
- Nimbolide: A Potential Phytochemical Agent in Multimodal Pancreatic Cancer Therapies.Mini reviews in medicinal chemistry · 2025Review
- The CXCR1 as a putative marker for cancer stem cell-like phenotypes in chemotherapy-resistant pancreatic ductal adenocarcinoma.American journal of cancer research · 2025Article
- Nanomedicine regulating PSC-mediated intercellular crosstalk: Mechanisms and therapeutic strategies.Acta pharmaceutica Sinica. B · 2024Review
- Unveiling the resistance to therapies in pancreatic ductal adenocarcinoma.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2024Review
- Targeting CD44 and other pleiotropic co-receptors as a means for broad inhibition of tumor growth and metastasis.Clinical & experimental metastasis · 2024Review
- Growth Hormone Receptor Antagonist Markedly Improves Gemcitabine Response in a Mouse Xenograft Model of Human Pancreatic Cancer.International journal of molecular sciences · 2024Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chemoresistance in pancreatic cancer cells may be caused by the expansion of inherently resistant cancer cells or by the adaptive plasticity of initially sensitive cancer cells. We investigated how CD44 isoforms switching contributed to gemcitabine resistance. Treating CD44 null/low single-cell clones with increasing amounts of gemcitabine caused an increase in expression of CD44 and development of gemcitabine resistant (GR) cells. Drug sensitivity, invasiveness, and EMT process was evaluated by MTT, Matrigel invasion assays, and western blots. Genetic knockdown and pharmacological inhibitors were used to examine the roles of CD44 and IGF1R in mediating gemcitabine resistance. CD44 promoter activity and its interactive EMT-related transcription factors were evaluated by luciferase reporter assay and chromatin immunoprecipitation assay. Kaplan-Meier curve was created by log-rank test to reveal the clinical relevance of CD44 and IGF1R expression in patients. We found silence of CD44 in GR cells partially restored E-cadherin expression, reduced ZEB1 expression, and increased drug sensitivity. The gemcitabine-induced CD44 expressing and isoform switching were associated with an increase in nuclear accumulation of phosphor-cJun, Ets1, and Egr1 and binding of these transcription factors to the CD44 promoter. Gemcitabine treatment induced phosphorylation of IGF1R and increased the expression of phosphor-cJun, Ets1, and Egr1 within 72 h. Stimulation or suppression of IGF1R signaling or its downstream target promoted or blocked CD44 promoter activity. Clinically, patients whose tumors expressed high levels of CD44/IGF1R showed a poor prognosis. This study suggests that IGF1R-dependent CD44 isoform switching confers pancreatic cancer cells to undergo an adaptive change in response to gemcitabine and provides the basis for improved targeted therapy of pancreatic cancer.
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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.