Sphingolipid Metabolism in Tumor Cells

Pokrovsky, Vadim S.; Иванова-Радкевич, В. И.; Кузнецова, О. М.

doi:10.1134/s0006297923070015

Cited by 1 publication

(2 citation statements)

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“…Disruption in lipid metabolism stands as one of the pivotal factors contributing to the onset, progression, and culmination of lung cancer. 3 , 4 Sphingolipids play a crucial role in tumor pathogenesis 5 , 6 and lipid metabolism. Consequently, our current comprehension regarding sphingolipid function in LC is still confined to a limited number of key players, especially in the LC microenvironment.…”

Section: Introductionmentioning

confidence: 99%

“… 10 , 11 In contrast, inhibiting ceramide biosynthesis and upregulating S1P through ceramide‐dependent signaling increased NSCLC in a disadvantageous situation. 5 , 12 In the tumor microenvironment, trained macrophages respond to lipopolysaccharide and stimulation of tumor‐derived soluble factors, which effectively controls tumor metastasis, with lung interstitial macrophages serving as the primary effector cells. 13 The activity of alkaline sphingomyelinase involves the sphingomyelin metabolites ceramide and S1P, which play a regulatory role in modulating the population of dendritic cells and T lymphocytes.…”

Section: Introductionmentioning

confidence: 99%

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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

Shen,

Liu,

et al. 2024

Thoracic Cancer

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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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