ArticleScientific reports2017
Inhibition of Sp1 prevents ER homeostasis and causes cell death by lysosomal membrane permeabilization in pancreatic cancer.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Links between the unfolded protein response and the DNA damage response in hypoxia: a systematic review.Biochemical Society transactions · 2021Pooled it
- The Link Between Endoplasmic Reticulum Stress and Lysosomal Dysfunction Under Oxidative Stress in Cancer Cells.Biomolecules · 2025Review
- 4-Phenylbutyric acid mitigates ER stress-induced neurodegeneration in the spinal cords of a GM2 gangliosidosis mouse model.Human molecular genetics · 2025Article
- Dominant missense variants in SREBF2 are associated with complex dermatological, neurological, and skeletal abnormalities.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Article
- Cytotoxic sigma-2 ligands trigger cancer cell death via cholesterol-induced-ER-stress.Cell death & disease · 2024Article
- Article
- Therapeutic potential of arginine deprivation therapy for gliomas: a systematic review of the existing literature.Frontiers in pharmacology · 2024Review
- Interaction and Collaboration of SP1, HIF-1, and MYC in Regulating the Expression of Cancer-Related Genes to Further Enhance Anticancer Drug Development.Current issues in molecular biology · 2023Review
- Review
- Integrated Bioinformatics Investigation of Novel Biomarkers of Uterine Leiomyosarcoma Diagnosis and Outcome.Journal of personalized medicine · 2023Article
- Comprehensive Analysis of Endoplasmic Reticulum Stress in Intracranial Aneurysm.Frontiers in cellular neuroscience · 2022Article
- Novel compound C150 inhibits pancreatic cancer through induction of ER stress and proteosome assembly.Frontiers in oncology · 2022Article
- Review
- Lysosomal Stress Response (LSR): Physiological Importance and Pathological Relevance.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2021Review
- microRNA-199a-5p regulates epithelial-to-mesenchymal transition in diabetic cataract by targeting SP1 gene.Molecular medicine (Cambridge, Mass.) · 2020Article
- Lumenal Galectin-9-Lamp2 interaction regulates lysosome and autophagy to prevent pathogenesis in the intestine and pancreas.Nature communications · 2020Article
- Betulinic Acid-Mediated Tuning of PERK/CHOP Signaling by Sp1 Inhibition as a Novel Therapeutic Strategy for Glioblastoma.Cancers · 2020Article
- Reduced miR-202 levels enhanced oral cancer development via targeting Sp1.Experimental and therapeutic medicine · 2019Article
- Specific protein 1(SP1) regulates the epithelial-mesenchymal transition via lysyl oxidase-like 2(LOXL2) in pancreatic ductal adenocarcinoma.Scientific reports · 2019Article
- GRP78-mediated antioxidant response and ABC transporter activity confers chemoresistance to pancreatic cancer cells.Molecular oncology · 2018Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Endoplasmic reticulum (ER) stress initiates an important mechanism for cell adaptation and survival, named the unfolded protein response (UPR). Severe or chronic/prolonged UPR can breach the threshold for survival and lead to cell death. There is a fundamental gap in knowledge on the molecular mechanism of how chronic ER stress is stimulated and leads to cell death in pancreatic ductal adenocarcinoma (PDAC). Our study shows that downregulating specificity protein 1 (Sp1), a transcription factor that is overexpressed in pancreatic cancer, activates UPR and results in chronic ER stress. In addition, downregulation of Sp1 results in its decreased binding to the ER stress response element present in the promoter region of Grp78, the master regulator of ER stress, thereby preventing homeostasis. We further show that inhibition of Sp1, as well as induction of ER stress, leads to lysosomal membrane permeabilization (LMP), a sustained accumulation of cytosolic calcium, and eventually cell death in pancreatic cancer.
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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.