ArticleThoracic cancer2024
Single-cell RNA sequencing reveals aberrant sphingolipid metabolism in non-small cell lung cancer impacts tumor-associated macrophages and stimulates angiogenesis via macrophage inhibitory factor signaling.
Article in Thoracic cancer, 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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Who cites it
12 citing papers in PubMed.
- Lipidomic Profiling Reveals Stage-Associated Triglyceride Accumulation in Macrophages in a Mouse Model of Ovarian Cancer.Cancers · 2026Article
- Tissue-Resident Macrophage in Inflammation and Cancer.MedComm · 2026Review
- Integrative single-cell and multi-omics analysis of ZBTB21-mediated serine metabolism in colorectal cancer: from metabolic reprogramming to immune microenvironment modulation.Cancer immunology, immunotherapy : CII · 2026Article
- SPP1+ Macrophages and the Orchestration of Spatially Organized Immunosuppression in Cancer.Biomedicines · 2026Review
- The Research Progress of Tumor-Associated Macrophages in Prostate Cancer.Journal of immunology research · 2026Review
- FABP4 in lipid metabolism and the tumor microenvironment: mechanisms and therapeutic potential.Lipids in health and disease · 2025Review
- [Plasma lipidomics-based exploration of potential biomarkers of metastasis in pediatric medulloblastoma].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2025Article
- Increased CDKN2A expression correlates with resistance to platinum-based therapy and decreased infiltration of B lymphocytes in colon adenocarcinoma.Functional & integrative genomics · 2025Article
- Machine Learning Unveils Sphingolipid Metabolism's Role in Tumour Microenvironment and Immunotherapy in Lung Cancer.Journal of cellular and molecular medicine · 2025Article
- Regulation of sphingolipid metabolism in the immune microenvironment of gastric cancer: current insights and future directions.Frontiers in oncology · 2025Review
- Sphingosine-1-phosphate stimulates colorectal cancer tumor microenvironment angiogenesis and induces macrophage polarization via macrophage migration inhibitory factor.Frontiers in immunology · 2025Article
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7 authors.
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Abstract
backgroundSphingolipids not only serve as structural components for maintaining cell membrane fluidity but also function as bioactive molecules involved in cell signaling and the regulation of various biological processes. Their pivotal role in cancer cell development, encompassing cancer cell proliferation, migration, angiogenesis, and metastasis, has been a focal point for decades. However, the contribution of sphingolipids to the complexity of tumor microenvironment promoting cancer progression has been rarely investigated.
methodsThrough the integration of publicly available bulk RNA-seq and single-cell RNA-seq data, we conducted a comprehensive analysis to compare the transcriptomic features between tumors and adjacent normal tissues, thus elucidating the intricacies of the tumor microenvironment (TME).
resultsDisparities in sphingolipid metabolism (SLM)-associated genes were observed between normal and cancerous tissues, with the TME characterized by the enrichment of sphingolipid signaling in macrophages. Cellular interaction analysis revealed robust communication between macrophages and cancer cells exhibiting low SLM, identifying the crucial ligand-receptor pair, macrophage inhibitory factor (MIF)-CD74. Pseudo-time analysis unveiled the involvement of SLM in modulating macrophage polarization towards either M1 or M2 phenotypes. Categorizing macrophages into six subclusters based on gene expression patterns and function, the SPP1+ cluster, RGS1+ cluster, and CXCL10+ cluster were likely implicated in sphingolipid-induced M2 macrophage polarization. Additionally, the CXCL10+, AGER+, and FABP4+ clusters were likely to be involved in angiogenesis through their interaction with endothelial cells.
conclusionBased on multiple scRNA-seq datasets, we propose that a MIF-targeted strategy could potentially impede the polarization from M1 to M2 and impair tumor angiogenesis in low-SLM non-small cell lung cancer (NSCLC), demonstrating its potent antitumor efficacy.
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