ArticleCancer biology & therapy2015
Differential regulation of autophagy and cell viability by ceramide species.
Article in Cancer biology & therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Metabolomics Analysis Uncovers Distinct Profiles of Liver Post-Transplant Patients by Immunosuppression Regimen.Metabolites · 2025Article
- Spinal muscular atrophy-like phenotype in a mouse model of acid ceramidase deficiency.Communications biology · 2023Article
- The Critical Impact of Sphingolipid Metabolism in Breast Cancer Progression and Drug Response.International journal of molecular sciences · 2023Review
- Restoration of atypical protein kinase C ζ function in autosomal dominant polycystic kidney disease ameliorates disease progression.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- 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
- Metabolome-Driven Regulation of Adenovirus-Induced Cell Death.International journal of molecular sciences · 2021Review
- Gb3-cSrc complex in glycosphingolipid-enriched microdomains contributes to the expression of p53 mutant protein and cancer drug resistance via β-catenin-activated RNA methylation.FASEB bioAdvances · 2020Article
- Beneficial Effects of Fingolimod in Alzheimer's Disease: Molecular Mechanisms and Therapeutic Potential.Neuromolecular medicine · 2019Review
- The Role of Ceramide and Sphingosine-1-Phosphate in Alzheimer's Disease and Other Neurodegenerative Disorders.Molecular neurobiology · 2019Review
- The Cross-Talk Between Sphingolipids and Insulin-Like Growth Factor Signaling: Significance for Aging and Neurodegeneration.Molecular neurobiology · 2019Review
- Fingolimod augments Pemetrexed killing of non-small cell lung cancer and overcomes resistance to ERBB inhibition.Cancer biology & therapy · 2019Article
- Impact of Autophagy in Oncolytic Adenoviral Therapy for Cancer.International journal of molecular sciences · 2017Review
- Role of P-glycoprotein inhibitors in ceramide-based therapeutics for treatment of cancer.Biochemical pharmacology · 2017Article
- Acid Ceramidase Deficiency in Mice Results in a Broad Range of Central Nervous System Abnormalities.The American journal of pathology · 2017Article
- Loss of neutral ceramidase protects cells from nutrient- and energy -deprivation-induced cell death.The Biochemical journal · 2016Article
- Ceramide Synthase 6 Is a Novel Target of Methotrexate Mediating Its Antiproliferative Effect in a p53-Dependent Manner.PloS one · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The present studies sought to determine whether the anti-folate pemetrexed (Alimta) and the sphingosine-1-phosphate receptor modulator FTY720 (Fingolimod, Gilenya) interacted to kill tumor cells. FTY720 and pemetrexed interacted in a greater than additive fashion to kill breast, brain and colorectal cancer cells. Loss of p53 function weakly enhanced the toxicity of FTY720 whereas deletion of activated RAS strongly or expression of catalytically inactive AKT facilitated killing. Combined drug exposure reduced the activity of AKT, p70 S6K and mTOR and activated JNK and p38 MAPK. Expression of activated forms of AKT, p70 S6K and mTOR or inhibition of JNK and p38 MAPK suppressed the interaction between FTY720 and pemetrexed. Treatment of cells with FTY720 and pemetrexed increased the numbers of early autophagosomes but not autolysosomes, which correlated with increased LC3II processing and increased p62 levels, suggestive of stalled autophagic flux. Knock down of ATG5 or Beclin1 suppressed autophagosome formation and cell killing. Knock down of ceramide synthase 6 suppressed autophagosome production and cell killing whereas knock down of ceramide synthase 2 enhanced vesicle formation and facilitated death. Collectively our findings argue that pemetrexed and FTY720 could be a novel adjunct modality for breast cancer treatment.
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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.