ArticleThe Biochemical journal2011
Sphingolipid-based drugs selectively kill cancer cells by down-regulating nutrient transporter proteins.
Article in The Biochemical journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 46 citations in OpenAlex.
- Sphingosine simultaneously inhibits nuclear import and activates PP2A by binding importins and PPP2R1A.The EMBO journal · 2025Article
- Mass Spectrometry Detects Sphingolipid Metabolites for Discovery of New Strategy for Cancer Therapy from the Aspect of Programmed Cell Death.Metabolites · 2023Review
- Molecular Pharmacology and Novel Potential Therapeutic Applications of Fingolimod.Frontiers in pharmacology · 2022Review
- TFEB phosphorylation on Serine 211 is induced by autophagy in human synovial fibroblasts and by p62/SQSTM1 overexpression in HEK293 cells.The Biochemical journal · 2021Article
- Synthetic Sphingolipids with 1,2-Pyridazine Appendages Improve Antiproliferative Activity in Human Cancer Cell Lines.ACS medicinal chemistry letters · 2020Article
- Metabolic Adaptation of Airway Smooth Muscle Cells to an SPHK2 Substrate Precedes Cytostasis.American journal of respiratory cell and molecular biology · 2020Article
- Ubiquitylation and endocytosis of the human LAT1/SLC7A5 amino acid transporter.Scientific reports · 2019Article
- FTY720 induces non-canonical phosphatidylserine externalization and cell death in acute myeloid leukemia.Cell death & disease · 2019Article
- Design, synthesis and anticancer activity of constrained sphingolipid-phenoxazine/phenothiazine hybrid constructs targeting protein phosphatase 2A.Bioorganic & medicinal chemistry letters · 2019Article
- Dynamic Phosphoproteomics Uncovers Signaling Pathways Modulated by Anti-oncogenic Sphingolipid Analogs.Molecular & cellular proteomics : MCP · 2019Article
- In search of constrained FTY720 and phytosphingosine analogs as dual acting anticancer agents targeting metabolic and epigenetic pathways.European journal of medicinal chemistry · 2018Article
- Sphingolipids inhibit endosomal recycling of nutrient transporters by inactivating ARF6.Journal of cell science · 2018Article
- TP53 is required for BECN1- and ATG5-dependent cell death induced by sphingosine kinase 1 inhibition.Autophagy · 2018Article
- Sphingosine-1-Phosphate Receptor-1 Promotes Environment-Mediated and Acquired Chemoresistance.Molecular cancer therapeutics · 2017Article
- FTY720-induced endocytosis of yeast and human amino acid transporters is preceded by reduction of their inherent activity and TORC1 inhibition.Scientific reports · 2017Article
- Phosphorylation of a constrained azacyclic FTY720 analog enhances anti-leukemic activity without inducing S1P receptor activation.Leukemia · 2017Article
- Sphingosine and Sphingosine Kinase 1 Involvement in Endocytic Membrane Trafficking.The Journal of biological chemistry · 2017Article
- Sphingosine kinase 1 is a potential therapeutic target for nasopharyngeal carcinoma.Oncotarget · 2016Article
- Targeting cancer metabolism by simultaneously disrupting parallel nutrient access pathways.The Journal of clinical investigation · 2016Article
- Aberrant expression of the S1P regulating enzymes, SPHK1 and SGPL1, contributes to a migratory phenotype in OSCC mediated through S1PR2.Scientific reports · 2016Article
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11 authors at 3 institutions in 1 country.
Funding
Abstract
Cancer cells are hypersensitive to nutrient limitation because oncogenes constitutively drive glycolytic and TCA (tricarboxylic acid) cycle intermediates into biosynthetic pathways. As the anaplerotic reactions that replace these intermediates are fueled by imported nutrients, the cancer cell's ability to generate ATP becomes compromised under nutrient-limiting conditions. In addition, most cancer cells have defects in autophagy, the catabolic process that provides nutrients from internal sources when external nutrients are unavailable. Normal cells, in contrast, can adapt to the nutrient stress that kills cancer cells by becoming quiescent and catabolic. In the present study we show that FTY720, a water-soluble sphingolipid drug that is effective in many animal cancer models, selectively starves cancer cells to death by down-regulating nutrient transporter proteins. Consistent with a bioenergetic mechanism of action, FTY720 induced homoeostatic autophagy. Cells were protected from FTY720 by cell-permeant nutrients or by reducing nutrient demand, but blocking apoptosis was ineffective. Importantly, AAL-149, a FTY720 analogue that lacks FTY720's dose-limiting toxicity, also triggered transporter loss and killed patient-derived leukaemias while sparing cells isolated from normal donors. As they target the metabolic profile of cancer cells rather than specific oncogenic mutations, FTY720 analogues such as AAL-149 should be effective against many different tumour types, particularly in combination with drugs that inhibit autophagy.
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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.