ArticleCell death & disease2019
ER stress sensor, glucose regulatory protein 78 (GRP78) regulates redox status in pancreatic cancer thereby maintaining "stemness".
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
79 citing papers in PubMed, 112 citations in OpenAlex.
- Resveratrol as a Bioactive Compound for Edible Fish Muscle Quality: Emerging Evidence, Putative Mechanisms, and Future Perspectives.Foods (Basel, Switzerland) · 2026Review
- p38β-mediated BiP phosphorylation drives stemness and chemoresistance by suppressing UPR activation in hepatocellular carcinoma.Nature communications · 2026Article
- A Radioresistant-Tumor-Targeted Nanoparticle for X-Ray-Controlled Nitric Oxide Release to Potentiate Radiotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Lipid Metabolism, Lipogenesis, and Resistance to Third Generation EGFR-TKIs.Journal of clinical laboratory analysis · 2026Review
- HSPA5 overexpression predicts poor prognosis and drives radioresistance and metastasis in nasopharyngeal carcinoma.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2026Article
- Mitochondria-targeted metformin analogs activate the ER stress-unfolded protein response pathway to drive apoptosis in pancreatic cancer.Cell death & disease · 2026Article
- Modulating Purothionin Accumulation and Signal Peptide Cleavage Fine-Tunes Wheat Flour Gluten Properties to Improve Cookie-Making Quality.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- GRP78 in human diseases: From molecular chaperone to therapeutic target.Theranostics · 2026Review
- Tumor-associated neutrophils in pancreatic ductal adenocarcinoma: mechanisms and therapeutic targeting.Frontiers in immunology · 2026Review
- Mechanotransduction-related ferroptosis: Enhancing boron neutron capture therapy efficacy in glioblastoma using a spheroid model.Molecular therapy. Oncology · 2025Article
- Artemisinin synergizes with CCCP in autophagic cell death induction via ER stress in uveal melanoma.iScience · 2025Article
- Endoplasmic Reticulum Stress in Cancer.MedComm · 2025Review
- Endoplasmic reticulum stress pathways and cellular death mechanisms in patients with phenylketonuria.Molecular biology reports · 2025Article
- Therapeutic potential of BOLD-100, a GRP78 inhibitor, enhanced by ATR inhibition in pancreatic ductal adenocarcinoma.Cell communication and signaling : CCS · 2025Article
- ER stress and/or ER-phagy in drug resistance? Three coincidences are proof.Cell communication and signaling : CCS · 2025Review
- Therapeutic limitations of oncolytic VSVd51-mediated miR-199a-5p delivery in triple negative breast cancer models.Scientific reports · 2025Article
- Sorafenib-Drug Delivery Strategies in Primary Liver Cancer.Journal of functional biomaterials · 2025Review
- Chemotherapy-Induced Cell-Surface GRP78 Expression as a Prognostic Marker for Invasiveness of Metastatic Triple-Negative Breast Cancer.Annals of biomedical engineering · 2025Article
- Malignant Pleural Mesothelioma: From Pathophysiology to Innovative Actionable Targets.Cancers · 2025Review
- PCSK1N as a Tumor Size Marker and an ER Stress Response Protein in Corticotroph Pituitary Adenomas.The Journal of clinical endocrinology and metabolism · 2025Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) signaling have been shown to be dysregulated in multiple cancer types. Glucose regulatory protein 78 (GRP78), the master regulator of the UPR, plays a role in proliferation, invasion, and metastasis in cancer. Cancer stem cells (CSCs) make up a crucial component of the tumor heterogeneity in pancreatic cancer, as well as other cancers. "Stemness" in pancreatic cancer defines a population of cells within the tumor that have increased therapeutic resistance as well as survival advantage. In the current study, we investigated how GRP78 was responsible for maintaining "stemness" in pancreatic cancer thereby contributing to its aggressive biology. We determined that GRP78 downregulation decreased clonogenicity and self-renewal properties in pancreatic cancer cell lines in vitro. In vivo studies resulted in delayed tumor initiation frequency, as well as smaller tumor volume in the shGRP78 groups. Additionally, downregulation of GRP78 resulted in dysregulated fatty acid metabolism in pancreatic tumors as well as the cells. Further, our results showed that shGRP78 dysregulates multiple transcriptomic and proteomic pathways that involve DNA damage, oxidative stress, and cell death, that were reversed upon treatment with a ROS inhibitor, N-acetylcysteine. This study thus demonstrates for the first time that the heightened UPR in pancreatic cancer may be responsible for maintenance of the "stemness" properties in these cells that are attributed to aggressive properties like chemoresistance and metastasis.
Indexed as
Identifiers
What OpenQuestion holds
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.