ArticleOncogene2012
Defining a role for sphingosine kinase 1 in p53-dependent tumors.
Article in Oncogene, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 73 citations in OpenAlex.
- An integrative approach to studying sphingolipid metabolism reveals p53 as a master regulator of the pathway.Journal of lipid research · 2026Article
- Molecular Mechanism and Research Progress of Sphingolipid Metabolism in Regulating Radiation-induced Apoptosis Using Pan-cancer Analysis.Current cancer drug targets · 2026Review
- Advances in ORMDL Research in Malignant Tumors: A Review.OncoTargets and therapy · 2025Review
- Targeting sphingosine kinase 1 in p53KO thymic lymphoma.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- The Metabolic Landscape of Breast Cancer and Its Therapeutic Implications.Molecular diagnosis & therapy · 2023Review
- The complexity of p53-mediated metabolic regulation in tumor suppression.Seminars in cancer biology · 2022Review
- Sphingolipid metabolism in the development and progression of cancer: one cancer's help is another's hindrance.Molecular oncology · 2021Review
- Bioactive sphingolipids: Advancements and contributions from the laboratory of Dr. Lina M. Obeid.Cellular signalling · 2021Review
- Dysregulation of lysophospholipid signaling by p53 in malignant cells and the tumor microenvironment.Cellular signalling · 2021Review
- Targeting sphingosine kinase 1 (SK1) enhances oncogene-induced senescence through ceramide synthase 2 (CerS2)-mediated generation of very-long-chain ceramides.Cell death & disease · 2021Article
- Ceramide Regulates Anti-Tumor Mechanisms of Erianin in Androgen-Sensitive and Castration-Resistant Prostate Cancers.Frontiers in oncology · 2021Article
- Article
- Identification of Plasma Glycosphingolipids as Potential Biomarkers for Prostate Cancer (PCa) Status.Biomolecules · 2020Article
- Lipid Players of Cellular Senescence.Metabolites · 2020Review
- Metabolic functions of the tumor suppressor p53: Implications in normal physiology, metabolic disorders, and cancer.Molecular metabolism · 2020Review
- Sphingosine Kinase 1 in Breast Cancer-A New Molecular Marker and a Therapy Target.Frontiers in oncology · 2020Review
- POTEE drives colorectal cancer development via regulating SPHK1/p65 signaling.Cell death & disease · 2019Article
- Anticancer effect of ursolic acid via mitochondria-dependent pathways.Oncology letters · 2019Review
- The Cross-Talk Between Sphingolipids and Insulin-Like Growth Factor Signaling: Significance for Aging and Neurodegeneration.Molecular neurobiology · 2019Review
- Links between accelerated replicative cellular senescence and down-regulation of SPHK1 transcription.BMB reports · 2019Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
p53 is a crucial tumor suppressor that is mutated or deleted in a majority of cancers. Exactly how p53 prevents tumor progression has proved elusive for many years; however, this information is crucial to define targets for chemotherapeutic development that can effectively restore p53 function. Bioactive sphingolipids have recently emerged as important regulators of proliferative, apoptotic and senescent cellular processes. In this study, we demonstrate that the enzyme sphingosine kinase 1 (SK1), a critical enzyme in the regulation of the key bioactive sphingolipids ceramide, sphingosine and sphingosine-1-phosphate (S1P), serves as a key downstream target for p53 action. Our results show that SK1 is proteolysed in response to genotoxic stress in a p53-dependent manner. p53 null mice display elevation of SK1 levels and a tumor-promoting dysregulation of bioactive sphingolipids in which the anti-growth sphingolipid ceramide is decreased and the pro-growth sphingolipid S1P is increased. Importantly, deletion of SK1 in p53 null mice completely abrogated thymic lymphomas in these mice and prolonged their life span by ~30%. Deletion of SK1 also significantly attenuated the formation of other cancers in p53 heterozygote mice. The mechanism of p53 tumor suppression by loss of SK1 is mediated by elevations of sphingosine and ceramide, which in turn were accompanied by increased expression of cell cycle inhibitors and tumor cell senescence. Thus, targeting SK1 may restore sphingolipid homeostasis in p53-dependent tumors and provide insights into novel therapeutic approaches to 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.