ArticleJournal of cell science2018
Sphingolipids inhibit endosomal recycling of nutrient transporters by inactivating ARF6.
Article in Journal of cell science, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- Endolysosomal trafficking regulator SH-BC-893 inhibits coronavirus entry in vitro and in vivo.Scientific reports · 2026Article
- Ceramide disrupts TM9SF2-PGK1 axis to redirect PD-L1 trafficking and enhance antitumor immunity.Nature communications · 2026Article
- Sphingolipid regulation by yeast Mdm1 supports adaptive remodeling of the methionine transporter Mup1.bioRxiv : the preprint server for biology · 2026Article
- TXNIP mediates LAT1/SLC7A5 endocytosis to limit amino acid uptake in cells entering quiescence.The EMBO journal · 2025Article
- Sphingosine simultaneously inhibits nuclear import and activates PP2A by binding importins and PPP2R1A.The EMBO journal · 2025Article
- Reconstitution of Rab11-FIP4 Expression Rescues Cellular Homeostasis in Cystinosis.Molecular and cellular biology · 2024Article
- Simultaneous inhibition of endocytic recycling and lysosomal fusion sensitizes cells and tissues to oligonucleotide therapeutics.Nucleic acids research · 2023Article
- The Lard Works in Mysterious Ways: Ceramides in Nutrition-Linked Chronic Disease.Annual review of nutrition · 2022Review
- Kir2.1-mediated membrane potential promotes nutrient acquisition and inflammation through regulation of nutrient transporters.Nature communications · 2022Article
- Review
- Drug-like sphingolipid SH-BC-893 opposes ceramide-induced mitochondrial fission and corrects diet-induced obesity.EMBO molecular medicine · 2021Article
- Blocking K-Ras Interaction With the Plasma Membrane Is a Tractable Therapeutic Approach to Inhibit Oncogenic K-Ras Activity.Frontiers in molecular biosciences · 2021Review
- Avicin G is a potent sphingomyelinase inhibitor and blocks oncogenic K- and H-Ras signaling.Scientific reports · 2020Article
- Synthetic Sphingolipids with 1,2-Pyridazine Appendages Improve Antiproliferative Activity in Human Cancer Cell Lines.ACS medicinal chemistry letters · 2020Article
- Ceramides: Nutrient Signals that Drive Hepatosteatosis.Journal of lipid and atherosclerosis · 2020Review
- FTY720 induces non-canonical phosphatidylserine externalization and cell death in acute myeloid leukemia.Cell death & disease · 2019Article
- Metabolic Messengers: ceramides.Nature metabolism · 2019Review
- Dynamic Phosphoproteomics Uncovers Signaling Pathways Modulated by Anti-oncogenic Sphingolipid Analogs.Molecular & cellular proteomics : MCP · 2019Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Endogenous sphingolipids (ceramide) and related synthetic molecules (FTY720, SH-BC-893) reduce nutrient access by decreasing cell surface expression of a subset of nutrient transporter proteins. Here, we report that these sphingolipids disrupt endocytic recycling by inactivating the small GTPase ARF6. Consistent with reported roles for ARF6 in maintaining the tubular recycling endosome, MICAL-L1-positive tubules were lost from sphingolipid-treated cells. We propose that ARF6 inactivation may occur downstream of PP2A activation since: (1) sphingolipids that fail to activate PP2A did not reduce ARF6-GTP levels; (2) a structurally unrelated PP2A activator disrupted tubular recycling endosome morphology and transporter localization; and (3) overexpression of a phosphomimetic mutant of the ARF6 GEF GRP1 prevented nutrient transporter loss. ARF6 inhibition alone was not toxic; however, the ARF6 inhibitors SecinH3 and NAV2729 dramatically enhanced the killing of cancer cells by SH-BC-893 without increasing toxicity to peripheral blood mononuclear cells, suggesting that ARF6 inactivation contributes to the anti-neoplastic actions of sphingolipids. Taken together, these studies provide mechanistic insight into how ceramide and sphingolipid-like molecules limit nutrient access and suppress tumor cell growth and survival.
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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.