ArticleAutophagy2018
TP53 is required for BECN1- and ATG5-dependent cell death induced by sphingosine kinase 1 inhibition.
Article in Autophagy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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.
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Who cites it
29 citing papers in PubMed, 43 citations in OpenAlex.
- Exploring Lipid Metabolic Reprogramming: Mechanistic Insights and Implications for Tumor Radiotherapy.International journal of biological sciences · 2026Review
- p53-regulated non-apoptotic cell death pathways and their relevance in cancer and other diseases.Nature reviews. Molecular cell biology · 2025Review
- The emerging roles of sphingosine 1-phosphate and SphK1 in cancer resistance: a promising therapeutic target.Cancer cell international · 2024Review
- The role of sphingosine-1-phosphate in autophagy and related disorders.Cell death discovery · 2023Review
- Isotretinoin treatment upregulates the expression of p53 in the skin and sebaceous glands of patients with acne vulgaris.Archives of dermatological research · 2023Article
- Anti-Alzheimers molecular mechanism of icariin: insights from gut microbiota, metabolomics, and network pharmacology.Journal of translational medicine · 2023Article
- Article
- Endoplasmic Reticulum Stress and Mitochondrial Stress in Drug-Induced Liver Injury.Molecules (Basel, Switzerland) · 2023Review
- Milk Exosomal microRNAs: Postnatal Promoters of β Cell Proliferation but Potential Inducers of β Cell De-Differentiation in Adult Life.International journal of molecular sciences · 2022Review
- The Role of Ceramide Metabolism and Signaling in the Regulation of Mitophagy and Cancer Therapy.Cancers · 2021Review
- lncRNA CASC19 Contributes to Radioresistance of Nasopharyngeal Carcinoma by Promoting Autophagy via AMPK-mTOR Pathway.International journal of molecular sciences · 2021Article
- Therapeutic Potential of SphK1 Inhibitors Based on Abnormal Expression of SphK1 in Inflammatory Immune Related-Diseases.Frontiers in pharmacology · 2021Review
- Analysis of selective target engagement by small-molecule sphingosine kinase inhibitors using the Cellular Thermal Shift Assay (CETSA).Cancer biology & therapy · 2020Article
- Manipulation of Mitophagy by "All-in-One" nanosensitizer augments sonodynamic glioma therapy.Autophagy · 2020Article
- Targeting defective sphingosine kinase 1 in Niemann-Pick type C disease with an activator mitigates cholesterol accumulation.The Journal of biological chemistry · 2020Article
- A simple method for sphingolipid analysis of tissues embedded in optimal cutting temperature compound.Journal of lipid research · 2020Article
- Sphingosine 1-Phosphate Signaling and Metabolism in Chemoprevention and Chemoresistance in Colon Cancer.Molecules (Basel, Switzerland) · 2020Review
- Regulatory role of SphK1 in TLR7/9-dependent type I interferon response and autoimmunity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Lysophospholipids and Their G-Coupled Protein Signaling in Alzheimer's Disease: From Physiological Performance to Pathological Impairment.Frontiers in molecular neuroscience · 2020Article
- Leptin stimulates autophagy/lysosome-related degradation of long-lived proteins in adipocytes.Adipocyte · 2019Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
The bioactive sphingolipid metabolite sphingosine-1-phosphate (S1P) and the enzyme that produces it, SPHK1 (sphingosine kinase 1), regulate many processes important for the etiology of cancer. It has been suggested that SPHK1 levels are regulated by the tumor suppressor protein TP53, a key regulator of cell cycle arrest, apoptosis, and macroautophagy/autophagy. However, little is still known of the relationship between TP53 and SPHK1 activity in the regulation of these processes. To explore this link, we examined the effects of inhibiting SPHK1 in wild-type and TP53 null cancer cell lines. SK1-I, an analog of sphingosine and isozyme-specific SPHK1 inhibitor, suppressed cancer cell growth and clonogenic survival in a TP53-dependent manner. It also more strongly enhanced intrinsic apoptosis in wild-type TP53 cells than in isogenic TP53 null cells. Intriguingly, SK1-I induced phosphorylation of TP53 on Ser15, which increases its transcriptional activity. Consequently, levels of TP53 downstream targets such as pro-apoptotic members of the BCL2 family, including BAX, BAK1, and BID were increased in wild-type but not in TP53 null cells. Inhibition of SPHK1 also increased the formation of autophagic and multivesicular bodies, and increased processing of LC3 and its localization within acidic compartments in a TP53-dependent manner. SK1-I also induced massive accumulation of vacuoles, enhanced autophagy, and increased cell death in an SPHK1-dependent manner that also required TP53 expression. Importantly, downregulation of the key regulators of autophagic flux, BECN1 and ATG5, dramatically decreased the cytotoxicity of SK1-I only in cells with TP53 expression. Hence, our results reveal that TP53 plays an important role in vacuole-associated cell death induced by SPHK1 inhibition in cancer cells.
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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.