ArticleMolecular cancer2015
Blockade of autophagy reduces pancreatic cancer stem cell activity and potentiates the tumoricidal effect of gemcitabine.
Article in Molecular cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers.
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Who cites it
114 citing papers in PubMed, 185 citations in OpenAlex.
- Phosphorylated STYK1 Promotes Gemcitabine Resistance via Autophagy-Mediated Cancer Stemness in Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Inhibiting Fatty Acid Oxidation Reverses Autophagy-Mediated Acquired Chemotherapy Resistance in Pancreatic Ductal Adenocarcinoma.Cancer research · 2026Article
- Dynamic ecosystems of tumor drug resistance mechanisms: from molecular heterogeneity to systemic interventions.Apoptosis : an international journal on programmed cell death · 2026Review
- E2F1-autophagy-ALDH1A1 axis enhances self-renewal and drug resistance of lung cancer stem-like cells in a p53-dependent manner.Journal of experimental & clinical cancer research : CR · 2025Article
- Hydroxychloroquine reduces metastatic tumor burden in pancreatic adenocarcinoma through myeloperoxidase inhibition.Journal of inflammation (London, England) · 2025Article
- USP10 promotes the progression and attenuates gemcitabine chemotherapy sensitivity via stabilizing PLK1 in PDAC.Cell death & disease · 2025Article
- The dual role of autophagy in cancer stem cells: implications for tumor progression and therapy resistance.Journal of translational medicine · 2025Review
- DAZAP1 maintains gastric cancer stemness by inducing mitophagy.JCI insight · 2025Article
- Therapeutic target prediction for orphan diseases integrating genome-wide and transcriptome-wide association studies.Nature communications · 2025Article
- CD44 variant exons induce chemoresistance by modulating cell death pathways.Frontiers in cell and developmental biology · 2025Review
- Osthole induces accumulation of impaired autophagosome against pancreatic cancer cells.Scientific reports · 2024Article
- Autophagy and cancer therapy.Cancer letters · 2024Review
- MicroRNA-mediated autophagy and drug resistance in cancer: mechanisms and therapeutic strategies.Discover oncology · 2024Review
- Multifaceted role ofMedComm · 2024Review
- OPN silencing reduces hypoxic pulmonary hypertension via PI3K-AKT-induced protective autophagy.Scientific reports · 2024Article
- Review
- ULK2 Is a Key Pro-Autophagy Protein That Contributes to the High Chemoresistance and Disease Relapse in FLT3-Mutated Acute Myeloid Leukemia.International journal of molecular sciences · 2024Article
- IL-13/IL-13RA2 signaling promotes colorectal cancer stem cell tumorigenesis by inducing ubiquitinated degradation of p53.Genes & diseases · 2024Article
- ISG15 Promotes Progression and Gemcitabine Resistance of Pancreatic Cancer Cells Through ATG7.International journal of biological sciences · 2024Article
- Immunohistochemical Expression of Autophagy-Related Marker (LC3B) and Stem Cell Marker (CD44) in Molecular Subtypes of Breast Cancer.Asian Pacific journal of cancer prevention : APJCP · 2024Article
54 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCancer stem cells (CSCs) are considered responsible for the recurrence and chemoresistance of cancer. Dysregulated autophagy is highly prevalent in many types of cancer including pancreatic cancer and has been implicated in cytoprotection and tumor promotion. This study aimed to investigate the role of autophagy in regulating cancer stemness and chemoresistance of pancreatic cancer.
methodsThe correlation between autophagy and CSCs and its clinical significance were analyzed using pancreatic cancer tissue microarrays. Genetic and pharmacological approaches were applied to explore the function of autophagy on CSC activity and gemcitabine resistance of pancreatic cancer cells in vitro and in vivo.
resultsLC3 expression positively correlated with the expression of CSC markers aldehyde dehydrogenase 1 (ALDH1), CD44, and CD133 in pancreatic cancer tissues. High coexpression of LC3/ALDH1 was associated with both poor overall survival and progression-free survival. In pancreatic cancer cell lines, higher LC3-II expression was observed in the sphere-forming cells than in the bulk cells. Blockade of autophagy by silencing ATG5, ATG7, and BECN1 or the administration of autophagy inhibitor chloroquine markedly reduced the CSC populations, ALDH1 activity, sphere formation, and resistance to gemcitabine in vitro and in vivo. Furthermore, osteopontin (OPN) was found to stimulate LC3-II, ALDH1, CD44, and CD133 expression in PANC-1 cells, whereas this effect could be prevented by OPN knockdown and autophagy blockade. After treatment with various inhibitors against the major signaling pathways downstream of OPN, only the inhibitor of NF-κB activation, BAY 1170-82, could effectively counteract OPN-induced autophagy and CSC activity. According to the histochemical results, pancreatic cancer patients manifesting high levels of OPN/LC3/ALDH1 and OPN/CD44/CD133 had poor survival.
conclusionsInduction of autophagy mediated by OPN/NF-κB signaling is required for maintenance of pancreatic CSC activity. Combination of gemcitabine with pharmacological autophagy inhibitors is a promising therapeutic strategy for 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.