ArticleBiochimica et biophysica acta. Molecular and cell biology of lipids2019
Upregulation of human glycolipid transfer protein (GLTP) induces necroptosis in colon carcinoma cells.
Article in Biochimica et biophysica acta. Molecular and cell biology of lipids, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 25 citations in OpenAlex.
- Predictive and mechanistic insights ofPeerJ · 2026Article
- Trigger Points of Necroptosis (RIPK1, RIPK3, and MLKL)-Promising Horizon or Blind Alley in Therapy of Colorectal Cancer?International journal of molecular sciences · 2025Review
- Use of Bicelle-Generated Lipid Bilayer Vesicle Nanoparticles for In Vitro Measurement of Lipid Intermembrane Transport.Methods in molecular biology (Clifton, N.J.) · 2025Article
- TRP-related gene signatures predict survival and the immune microenvironment in rectal cancer: a comprehensive bioinformatics study.Frontiers in immunology · 2025Article
- Crosstalk between metabolism and cell death in tumorigenesis.Molecular cancer · 2024Review
- Exploration of the mechanism of reinfusion of fresh autologous blood in type 2 diabetes mice to induce macrophage polarization and inhibit erythrocyte damage.Journal of diabetes investigation · 2024Article
- Ferroptosis, Necroptosis, and Pyroptosis in Gastrointestinal Cancers: The Chief Culprits of Tumor Progression and Drug Resistance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- Skewing cPLAScience signaling · 2023Article
- Emergence of the fungal immune system.iScience · 2023Review
- Non-Canonical Programmed Cell Death in Colon Cancer.Cancers · 2022Review
- miR-196a Upregulation Contributes to Gefitinib Resistance through Inhibiting GLTP Expression.International journal of molecular sciences · 2022Article
- Immune infiltration and a necroptosis-related gene signature for predicting the prognosis of patients with cervical cancer.Frontiers in genetics · 2022Article
- GLTP Is a Potential Prognostic Biomarker and Correlates with Immunotherapy Efficacy in Cervical Cancer.Disease markers · 2022Article
- Ceramide-1-phosphate transfer protein promotes sphingolipid reorientation needed for binding during membrane interaction.Journal of lipid research · 2022Article
- GDC-0326 Enhances the Effects of 5-Fu in Colorectal Cancer Cells by Inducing Necroptotic Death.OncoTargets and therapy · 2021Article
- Receptor-interacting protein in malignant digestive neoplasms.Journal of Cancer · 2021Review
- Metabolism of Glycosphingolipids and Their Role in the Pathophysiology of Lysosomal Storage Disorders.International journal of molecular sciences · 2020Review
- Emerging roles for human glycolipid transfer protein superfamily members in the regulation of autophagy, inflammation, and cell death.Progress in lipid research · 2020Review
- Review
- Sphingolipid-Transporting Proteins as Cancer Therapeutic Targets.International journal of molecular sciences · 2019Review
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Authors and funding
4 authors at 4 institutions in 1 country.
Funding
Abstract
Human GLTP on chromosome 12 (locus 12q24.11) encodes a 24 kD amphitropic lipid transfer protein (GLTP) that mediates glycosphingolipid (GSL) intermembrane trafficking and regulates GSL homeostatic levels within cells. Herein, we provide evidence that GLTP overexpression inhibits the growth of human colon carcinoma cells (HT-29; HCT-116), but spares normal colonic cells (CCD-18Co). Mechanistic studies reveal that GLTP overexpression arrested the cell cycle at the G1/S checkpoint via upregulation of cyclin-dependent kinase inhibitor-1B (Kip1/p27) and cyclin-dependent kinase inhibitor 1A (Cip1/p21) at the protein and mRNA levels, and downregulation of cyclin-dependent kinase-2 (CDK2), cyclin-dependent kinase-4 (CDK4), cyclin E and cyclin D1 protein levels. Assessment of the biological fate of HCT-116 cells overexpressing GLTP indicated no increase in cell death suggesting induction of quiescence. However, HT-29 cells overexpressing GLTP underwent cell death by necroptosis as revealed by phosphorylation of human mixed lineage kinase domain-like protein (pMLKL) via receptor-interacting protein kinase-3 (RIPK-3), elevated cytosolic calcium, and plasma membrane permeabilization by pMLKL oligomerization. Overexpression of W96A-GLTP, an ablated GSL binding site mutant, failed to arrest the cell cycle or induce necroptosis. Sphingolipid assessment (ceramide, monohexosylceramide, sphingomyelin, ceramide-1-phosphate, sphingosine, and sphingosine-1-phosphate) of HT-29 cells overexpressing GLTP revealed large decreases (>5-fold) in sphingosine-1-phosphate with minimal change in 16:0-ceramide, tipping the 'sphingolipid rheostat' (S1P/16:0-Cer ratio) towards cell death. Depletion of RIPK-3 or MLKL abrogated necroptosis induced by GLTP overexpression. Our findings establish GLTP upregulation as a previously unknown suppressor of human colon carcinoma HT-29 cells via interference with cell cycle progression and induction of necroptosis.
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