ArticleProceedings of the National Academy of Sciences of the United States of America2009
Intracellular cleavage of osteopontin by caspase-8 modulates hypoxia/reoxygenation cell death through p53.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 42 citations in OpenAlex.
- Context-dependent roles of osteopontin in aging-related neurological disorders.The Journal of international medical research · 2026Review
- The Multifaceted Role of Osteopontin in Prostate Pathologies.Biomedicines · 2023Review
- Osteopontin (OPN)/SPP1: from its biochemistry to biological functions in the innate immune system and the central nervous system (CNS).International immunology · 2023Review
- Both Full-Length and Protease-Cleaved Products of Osteopontin Are Elevated in Infectious Diseases.Biomedicines · 2021Review
- Osteopontin as a Regulator of Colorectal Cancer Progression and Its Clinical Applications.Cancers · 2021Review
- Stimulation of THP-1 Macrophages with LPS Increased the Production of Osteopontin-Encapsulating Exosome.International journal of molecular sciences · 2020Article
- Ameliorating Effect of Osteopontin on HCellular and molecular neurobiology · 2018Article
- Angiotensin 1-7, but not the thrombin-cleaved osteopontin C-terminal fragment, attenuates osteopontin-mediated macrophage-induced endothelial-cell inflammation.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2018Article
- Phosphorylated CAV1 activates autophagy through an interaction with BECN1 under oxidative stress.Cell death & disease · 2017Article
- Spatiotemporal expression of osteopontin in the striatum of rats subjected to the mitochondrial toxin 3-nitropropionic acid correlates with microcalcification.Scientific reports · 2017Article
- Osteopontin Fragments with Intact Thrombin-Sensitive Site Circulate in Cervical Cancer Patients.PloS one · 2016Article
- Hypoxia accelerates vascular repair of endothelial colony-forming cells on ischemic injury via STAT3-BCL3 axis.Stem cell research & therapy · 2015Article
- Article
- Osteopontin deficiency aggravates hepatic injury induced by ischemia-reperfusion in mice.Cell death & disease · 2014Article
- Hypoxia-driven osteopontin contributes to breast tumor growth through modulation of HIF1α-mediated VEGF-dependent angiogenesis.Oncogene · 2014Article
- Role of hepatitis C virus induced osteopontin in epithelial to mesenchymal transition, migration and invasion of hepatocytes.PloS one · 2014Article
- Arrestins in apoptosis.Handbook of experimental pharmacology · 2014Article
- The dual role of osteopontin in acetaminophen hepatotoxicity.Acta pharmacologica Sinica · 2012Article
- The mitochondrial component of intracrine action.American journal of physiology. Heart and circulatory physiology · 2010Review
- Osteopontin is cleaved at multiple sites close to its integrin-binding motifs in milk and is a novel substrate for plasmin and cathepsin D.The Journal of biological chemistry · 2010Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteopontin (OPN) is highly expressed in cancer patients and plays important roles in many stages of tumor progression, such as anti-apoptosis, proliferation, and metastasis. From functional screening of human cDNA library, we isolated OPN as a caspase-8 substrate that regulates cell death during hypoxia/reoxygenation (Hyp/RO). In vitro cleavage assays demonstrate that OPN is cleaved at Asp-135 and Asp-157 by caspase-8. Cellular cleavage of OPN is observed in apoptotic cells exposed to Hyp/RO among various apoptotic stimuli and its cleavage is blocked by zVAD or IETD caspase inhibitor. Further, over-expression of OPN, the form with secretion signal, inhibits Hyp/RO-induced cell death. Caspase cleavage-defective OPN mutant (OPN D135A/D157A) is more efficient to suppress Hyp/RO-induced cell death than wild-type OPN. OPN D135A/D157A sustains AKT activity to increase cell viability through inhibition of caspase-9 during Hyp/RO. In addition, OPN is highly induced in some tumor cells during Hyp/RO, such as HeLa and Huh-7 cells, which is associated with their resistance to Hyp/RO by sustaining AKT activity. Notably, OPN C-terminal cleavage fragment produced by caspase-8 is detected in the nucleus. Plasmid-encoded expression of OPN C-terminal cleavage fragment increases p53 protein level and induces apoptosis of wild-type mouse embryonic fibroblast cells, but not p53(-/-) mouse embryonic fibroblast cells. These observations suggest that the protective function of OPN during Hyp/RO is inactivated via the proteolytic cleavage by caspase-8 and its cleavage product subsequently induces cell death via p53, postulating caspase-8 as a negative regulator of tumorigenic activity of OPN.
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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.