ArticleCell2009
The tumor suppressor Par-4 activates an extrinsic pathway for apoptosis.
Article in Cell, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 131 papers.
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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
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Who cites it
131 citing papers in PubMed.
- RNF5 promotes acute lung injury through HSPA5 ER-to-cytosol translocation and resultant PERK activation.Cell death and differentiation · 2026Article
- PAWR augments anti-RNA viral innate immunity by promoting the PIM2-XBP1s-RIG-I signaling axis.Nature communications · 2026Article
- RCN3 functions as a tumor promoter in colorectal cancer by modulating the GRP78-PI3K-AKT signaling pathway.Oncogene · 2025Article
- Stress-induced translocation of the endoplasmic reticulum chaperone GRP78/BiP and its impact on human disease and therapy.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Endoplasmic Reticulum Stress in Cancer.MedComm · 2025Review
- Turn TRAIL Into Better Anticancer Therapeutic Through TRAIL Fusion Proteins.Cancer medicine · 2025Review
- The Tumor Suppressor Par-4 Regulates Adipogenesis by Transcriptional Repression of PPARγ.Cells · 2024Article
- Antitumor Efficacy of Arylquin 1 through Dose-Dependent Cytotoxicity, Apoptosis Induction, and Synergy with Radiotherapy in Glioblastoma Models.Biomedicines · 2024Article
- A computational peptide model induces cancer cells' apoptosis by docking Kringle 5 to GRP78.BMC molecular and cell biology · 2023Article
- Aberrant LYZ expression in tumor cells serves as the potential biomarker and target for HCC and promotes tumor progression via csGRP78.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- HSPA5 Promotes Attachment and Internalization of Porcine Epidemic Diarrhea Virus through Interaction with the Spike Protein and the Endo-/Lysosomal Pathway.Journal of virology · 2023Article
- Enhancing the Conformational Stability of the cl-Par-4 Tumor Suppressor via Site-Directed Mutagenesis.Biomolecules · 2023Article
- The regulatory mechanisms and inhibitors of isocitrate dehydrogenase 1 in cancer.Acta pharmaceutica Sinica. B · 2023Review
- The therapeutic mavericks: Potent immunomodulating chaperones capable of treating human diseases.Journal of cellular and molecular medicine · 2023Review
- Crizotinib induces Par-4 secretion from normal cells and GRP78 expression on the cancer cell surface for selective tumor growth inhibition.American journal of cancer research · 2023Article
- The endoplasmic reticulum stress response in prostate cancer.Nature reviews. Urology · 2022Review
- Protein Disulfide Isomerases Function as the Missing Link Between Diabetes and Cancer.Antioxidants & redox signaling · 2022Review
- Potential to Eradicate Cancer Stemness by Targeting Cell Surface GRP78.Biomolecules · 2022Review
- Decoy receptor 2 mediates the apoptosis-resistant phenotype of senescent renal tubular cells and accelerates renal fibrosis in diabetic nephropathy.Cell death & disease · 2022Article
- Arylquin 1 (Potent Par-4 Secretagogue) Inhibits Tumor Progression and Induces Apoptosis in Colon Cancer Cells.International journal of molecular sciences · 2022Article
71 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
6 authors.
Funding
Abstract
Prostate apoptosis response-4 (Par-4) is a proapoptotic protein with intracellular functions in the cytoplasm and nucleus. Unexpectedly, we noted Par-4 protein is spontaneously secreted by normal and cancer cells in culture, and by Par-4 transgenic mice that are resistant to spontaneous tumors. Short exposure to endoplasmic reticulum (ER) stress-inducing agents further increased cellular secretion of Par-4 by a brefeldin A-sensitive pathway. Secretion occurred independently of caspase activation and apoptosis. Interestingly, extracellular Par-4 induced apoptosis by binding to the stress response protein, glucose-regulated protein-78 (GRP78), expressed at the surface of cancer cells. The interaction of extracellular Par-4 and cell surface GRP78 led to apoptosis via ER stress and activation of the FADD/caspase-8/caspase-3 pathway. Moreover, apoptosis inducible by TRAIL, which also exerts cancer cell-specific effects, is dependent on extracellular Par-4 signaling via cell surface GRP78. Thus, Par-4 activates an extrinsic pathway involving cell surface GRP78 receptor for induction of apoptosis.
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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.