ArticleCell reports2024
Alterations of ceramide synthesis induce PD-L1 internalization and signaling to regulate tumor metastasis and immunotherapy response.
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Article in Cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed.
- Lysyl oxidase inhibition disrupts mitochondrial homeostasis to create vulnerability to ferroptosis in TNBC.Cell reports. Medicine · 2026Article
- Tumor and Stromal Sphingolipid Imbalance Are Associated with T Cell Tissue Residency in Glioblastoma.Cancers · 2026Article
- Depression-induced systemic C16-ceramide deficiency promotes OSCC via attenuation of mitochondrial apoptosis.Cellular and molecular life sciences : CMLS · 2026Article
- Diverse high-fat diets drive multi-omic reprogramming that persists after dietary reversal.bioRxiv : the preprint server for biology · 2026Article
- Sphingolipid metabolism-related genes B4GALNT1 and CERS4 as prognostic biomarkers in lung adenocarcinoma.PloS one · 2026Article
- The tumor microenvironment of medulloblastoma: from emerging biological insights to novel therapeutic targeting.Frontiers in oncology · 2026Review
- A chemokine-based prognostic model featuring CXCL8, ITGA5, BACE2, CCR7, CERS4, and MEI1 for cervical cancer.European journal of medical research · 2025Article
- Alzheimer's Disease-Associated Amyloid-β Precursor Protein Prevents Aging Stress-Induced Mitophagy and Fumarate Depletion to Improve Antitumor Immunity.Cancer research · 2025Article
- Microbial riboflavin inhibits ceramide synthase 3 to lower ceramide (d18:1/26:0) and delay colorectal cancer progression.Cell metabolism · 2025Article
- Ceramide signaling in immunity: a molecular perspective.Lipids in health and disease · 2025Review
- Immunotherapy resistance in triple-negative breast cancer: Molecular mechanisms, tumor microenvironment, and therapeutic implications.Frontiers in oncology · 2025Review
- Integrating Single-Cell and Bulk RNA Sequencing Data to Explore Sphingolipid Metabolism Molecular Signatures in Ovarian Cancer Prognosis: an Original Study.International journal of medical sciences · 2025Article
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Authors and funding
17 authors.
Wyatt WoffordDepartment of Biochemistry and Molecular Biology, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA.
Jisun KimDepartment of Biochemistry and Molecular Biology, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA.
Dosung KimDepartment of Biochemistry and Molecular Biology, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA.
Alhaji H JannehDepartment of Biochemistry and Molecular Biology, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA.
Han Gyul LeeDepartment of Biochemistry and Molecular Biology, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA.
F Cansu AtilganDepartment of Biochemistry and Molecular Biology, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA.
Natalia OleinikDepartment of Biochemistry and Molecular Biology, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA.
Mohamed Faisal KassirDepartment of Biochemistry and Molecular Biology, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA.
Ozge SaatciDepartment of Biochemistry and Molecular Biology, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA.
Paramita ChakrabortyDepartment of Biochemistry and Molecular Biology, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Department of Surgery, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA.
Unal Metin TokatDepartment of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey.
Salih GencerDepartment of Biochemistry and Molecular Biology, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Istanbul Medipol University, Health Science and Technologies Research Institute (SABİTA), Cancer Research Center, Istanbul, Turkey.
Breege HowleyDepartment of Biochemistry and Molecular Biology, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA.
Philip HoweDepartment of Biochemistry and Molecular Biology, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA.
Shikhar MehrotraDepartment of Biochemistry and Molecular Biology, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Department of Surgery, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA.
Ozgur SahinDepartment of Biochemistry and Molecular Biology, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA.
Besim OgretmenDepartment of Biochemistry and Molecular Biology, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA. Electronic address: ogretmen@musc.edu.
Funding
Translational Science Laboratory Shared ResourceP30CA138313 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI Jian Ouyang · 2009 to 2026
$42.7MProject 3: Targeting SK2/S1P Signaling for the Regulation of c-Myc and Tumor SuppressionP01CA203628 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI BIELAWSKA, ALICJA · 2016 to 2021
$8.9MCeramide Signaling in the Regulation of Head & Neck Cancer Cell Death and TherapyR01DE016572 · NIDCR · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI OGRETMEN, BESIM · 2005 to 2025
$7.4MRESEARCH PILOT PROJECTS PROGRAMP30GM103339 · NIGMS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI CROSSON, CRAIG E. · 2012 to 2016
$5.4MResearch Supplement to Promote Diversity in Health-Related ResearchR01CA214461 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI Besim Ogretmen · 2018 to 2026
$3.3MMUSC FACIL EXPANSION &RENOV: SLE C06RR015455 · NCRR · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI RAYMOND, JOHN R · 2002 to 2002
$2.0MTargeting cytoplasmic SET oncoprotein by sphingolipid analog drugs for the induction of necroptosis to treat lung cancerR01CA285926 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI Besim Ogretmen · 2024 to 2026
$1.9MNCI NIH HHS P01 CA203628NCI NIH HHS P30 CA138313NCI NIH HHS R01 CA214461NCI NIH HHS R01 CA285926NCRR NIH HHS C06 RR015455NIDCR NIH HHS R01 DE016572NIGMS NIH HHS P30 GM103339
Abstract
Programmed death ligand 1, PD-L1 (CD274), facilitates immune evasion and exerts pro-survival functions in cancer cells. Here, we report a mechanism whereby internalization of PD-L1 in response to alterations of bioactive lipid/ceramide metabolism by ceramide synthase 4 (CerS4) induces sonic hedgehog (Shh) and transforming growth factor β receptor signaling to enhance tumor metastasis in triple-negative breast cancers (TNBCs), exhibiting immunotherapy resistance. Mechanistically, data showed that internalized PD-L1 interacts with an RNA-binding protein, caprin-1, to stabilize Shh/TGFBR1/Wnt mRNAs to induce β-catenin signaling and TNBC growth/metastasis, consistent with increased infiltration of FoxP3
Indexed as
B7-H1 AntigenCeramidesImmunotherapyNeoplasm MetastasisSignal TransductionAnimalsCell Line, TumorFemaleHedgehog ProteinsHumansMiceTriple Negative Breast NeoplasmsB7-H1 AntigenCD274 protein, humanCeramidesHedgehog ProteinsceramideCerS4CP: CancerCP: MetabolismimmunotherapymetastasisPD-L1sonic hedgehogsphingolipid
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