ArticleOncotarget2015
Hypoxia-induced endoplasmic reticulum stress characterizes a necrotic phenotype of pancreatic cancer.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 44 citations in OpenAlex.
- Tumor-to-anterior pancreas surface distance on CT: a potential preoperative predictor of resection margin status in pancreatic body and tail adenocarcinoma.European radiology · 2026Article
- Tumor-associated neutrophils in pancreatic ductal adenocarcinoma: mechanisms and therapeutic targeting.Frontiers in immunology · 2026Review
- Therapeutic potential of BOLD-100, a GRP78 inhibitor, enhanced by ATR inhibition in pancreatic ductal adenocarcinoma.Cell communication and signaling : CCS · 2025Article
- Preoperative Prognostic Factors in Resectable Pancreatic Cancer: State of the Art and Prospects.Annals of surgical oncology · 2025Review
- Sphingosine-1-Phosphate Inhibition Increases Endoplasmic Reticulum Stress to Enhance Oxaliplatin Sensitivity in Pancreatic Cancer.World journal of oncology · 2024Article
- Radiomics analysis with three-dimensional and two-dimensional segmentation to predict survival outcomes in pancreatic cancer.World journal of radiology · 2023Article
- A risk signature based on endoplasmic reticulum stress-associated genes predicts prognosis and immunity in pancreatic cancer.Frontiers in molecular biosciences · 2023Article
- Increasing Stress to Induce Apoptosis in Pancreatic Cancer via the Unfolded Protein Response (UPR).International journal of molecular sciences · 2022Review
- Promotion of osteogenesis in BMSC under hypoxia by ATF4 via the PERK-eIF2α signaling pathway.In vitro cellular & developmental biology. Animal · 2022Article
- SET/PP2A signaling regulates macrophage positioning in hypoxic tumor regions by amplifying chemotactic responses.Experimental & molecular medicine · 2022Article
- Review
- Article
- Melatonin Induces Apoptosis and Modulates Cyclin Expression and MAPK Phosphorylation in Pancreatic Stellate Cells Subjected to Hypoxia.International journal of molecular sciences · 2021Article
- Hypoxia promotes the metastasis of pancreatic cancer through regulating NOX4/KDM5A-mediated histone methylation modification changes in a HIF1A-independent manner.Clinical epigenetics · 2021Article
- Review
- PPARγ/SOD2 Protects Against Mitochondrial ROS-Dependent Apoptosis via Inhibiting ATG4D-Mediated Mitophagy to Promote Pancreatic Cancer Proliferation.Frontiers in cell and developmental biology · 2021Article
- Homocysteine promotes hepatic steatosis by activating the adipocyte lipolysis in a HIF1α-ERO1α-dependent oxidative stress manner.Redox biology · 2020Article
- ALDH1A3 Accelerates Pancreatic Cancer Metastasis by Promoting Glucose Metabolism.Frontiers in oncology · 2020Article
- Sea Cucumber (Nutrients · 2019Article
- Comprehensive analysis of differentially expressed non-coding RNAs and mRNAs in gastric cancer cells under hypoxic conditions.American journal of translational research · 2018Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stromal fibrosis and tissue necrosis are major histological sequelae of hypoxia. The hypoxia-to-fibrosis sequence is well-documented in pancreatic ductal adenocarcinoma (PDAC). However, hypoxic and necrotic PDAC phenotypes are insufficiently characterized. Recently, reduction of tuberous sclerosis expression in mice together with oncogenic Kras demonstrated a rapidly metastasizing phenotype with histologically eccentric necrosis, transitional hypoxia and devascularisation. We established cell lines from these tumors and transplanted them orthotopically into wild-type mice to test their abilities to recapitulate the histological features of the primary lesions. Notably, the necrotic phenotype was reproduced by only a subset of cell lines while others gave rise to dedifferentiated tumors with significantly reduced necrosis. In vitro analysis of the necrotic tumor-inducing cell lines revealed that these cells released a significant amount of vascular endothelial growth factor A (Vegfa). However, its release was not further increased under hypoxic conditions. Defective hypoxia-induced Vegfa secretion was not due to impaired Vegfa transcription or hypoxia-inducible factor 1-alpha activation, but rather a result of hypoxia-induced endoplasmic reticulum (ER) stress. We thus identified hypoxia-induced ER stress as an important pathway in PDACs with tissue necrosis and rapid metastasis.
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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.