The ceramide synthase (CERS/LASS) family: Functions involved in cancer progression

Zhang, Mengmeng; Li, Zhangyun; Liu, Yuwei; Ding, Xiao; Wang, Yanyan; Fan, Shao‐Hua

doi:10.1007/s13402-023-00798-6

Cited by 9 publications

(5 citation statements)

References 116 publications

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“…Subsequently, sphingosine is phosphorylated by sphingosine kinases (SPHK) to give rise to sphingosine-1-phosphate (S1P). Several literature data support the involvement of CerS, CERK and SPHK in PCa biology 32 , 33 , and some studies suggest that enhanced ceramide-S1P signaling may mediate ARSi resistance induced by AR gain 34 .…”

Section: Discussionmentioning

confidence: 85%

Untargeted lipidomics reveal association of elevated plasma C18 ceramide levels with reduced survival in metastatic castration-resistant prostate cancer patients

Cattrini,

Manfredi,

Barboro

et al. 2023

Sci Rep

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Emerging evidence highlights the potential prognostic relevance of circulating lipids in metastatic castration-resistant prostate cancer (mCRPC), with a proposed 3-lipid signature. This study aims to analyze the lipidomic profiles of individuals with mCRPC to identify lipid species that could serve as predictive indicators of prognosis and therapeutic response. Plasma samples were collected from mCRPC patients initiating first-line treatment (1 L) (n = 29) and those previously treated with at least two lines of therapy (> 2 L) (n = 19), including an androgen-receptor signaling inhibitor and a taxane. Employing an untargeted lipidomic approach, lipids were extracted from the plasma samples and subjected to analysis. A comprehensive identification and quantification of 789 plasma lipids was achieved. Notably, 75 species displayed significant dysregulation in > 2 L patients in comparison to the 1 L group. Among these, 63 species exhibited elevated levels, while 12 were reduced. Patients included in > 2 L cohort showed elevated levels of acylcarnitines (CAR), diacylglycerols (DG), phosphatidylethanolamines (PE), triacylglycerols (TG), and ceramides (Cer). Notably, some upregulated lipids, including CAR 14:0, CAR 24:1, Cer d18:1/16:0, Cer d18:1/18:0 (C18 Cer), Cer d18:2/18:0, Cer d18:1/24:1, and Cer d20:1/24:1, showed significant associations with overall survival (OS) in univariate models. Specifically, increased levels of C18 Cer remained significantly associated with poorer OS in the multivariate model, even after adjusting for treatment line and PSA levels (Hazard Ratio: 3.59 [95% Confidence Interval 1.51–8.52], p = 0.004). Employing quantitative mass spectrometry, our findings underscore the independent prognostic significance of C18 Cer in individuals with mCRPC. This discovery opens avenues for further studies within this field.

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Section: Discussionmentioning

confidence: 85%

Untargeted lipidomics reveal association of elevated plasma C18 ceramide levels with reduced survival in metastatic castration-resistant prostate cancer patients

Cattrini,

Manfredi,

Barboro

et al. 2023

Sci Rep

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“…Further mutation analysis showed that somatic mutations were more prevalent in TNE than in stroma and identified four genes containing top SNPs with somatic mutations. Among these genes, Cers2 plays a vital role in preserving hepatic chromosome polyploidization during cell division by regulating the expression of Mad2 in mouse [79], and is closely associated with the progression of liver cancer [80]. Takeda et al [81] reported that ETS2 functions as a key downstream transcription factor and assembles a transcription complex with MLL in HCC cells that directly activates MMP1 and MMP3 .…”

Section: Discussionmentioning

confidence: 99%

FAST: a fast and scalable factor analysis for spatially aware dimension reduction of multi-section spatial transcriptomics data

Liu

Zhang

Chai

et al. 2023

Preprint

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Biological techniques for spatially resolved transcriptomics (SRT) have advanced rapidly in both throughput and spatial resolution for a single spatial location. This progress necessitates the development of efficient and scalable spatial dimension reduction methods that can handle large-scale SRT data from multiple sections. Here, we developed ProFAST as a fast and efficient probabilistic factor analysis for spatially aware dimension reduction, which simultaneously extracts a low-dimensional representation of SRT data across multiple sections, while preserving biological effects with consideration of spatial smoothness among nearby locations. Compared with existing methods, ProFAST is applicable to SRT data across multiple sections while using a local spatial dependence with scalable computational complexity. Using both simulated and real datasets, we demonstrated the improved correlation between ProFAST estimated embeddings and annotated cell/domain types. Furthermore, ProFAST exhibits remarkable speed, being >700 times faster, and requiring only 3% of the memory compared to the well-established tool, SpatialPCA, when applied to a Xenium dataset. Indeed, ProFAST was used to analyze a mouse embryo Stereo-seq dataset with >2.3 million locations in only 2 hours. More importantly, ProFAST identified differential activities of immune-related transcription factors between tumor and non-tumor clusters and also predicted a carcinogenesis factor CCNH as the upstream regulator of differentially expressed genes in a breast cancer Xenium dataset.

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“…Furthermore, both molecules are quantitatively reduced after treatment with VitC suggesting a possible reduction of synthesis rather than an activation of catabolism. It is known that Cer synthase is involved in cancer progression [43] and induces chemoresistance [44]. Therefore, the role of VitC in limiting the metastatic spread of triple negative cancer cannot be excluded.…”

Section: Discussionmentioning

confidence: 99%

Vitamin C Modifies the Phenotype of Hormone Receptor Positive/HER2 Negative Breast Cancer Cells and Induces Changes in Sphingolipid Metabolism

Codini¹,

Fiorani²,

Mandarano³

et al. 2023

Preprint

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The effect of the antioxidant vitamin C in cancer has been studied for over 30 years with conflict-ing results ranging from total absence of effect, to possible protective effect, to potential therapeutic effect when administered in high doses. The aim of the study was to define the effect of vitamin C in breast cancer and the possible involvement of sphingomyelin metabolism. Therefore, the effect of low and high dose of vitamin C on cells reproducing luminal A type (MCF7) and triple negative type (MB231) of breast cancer was analyzed. The results showed that high dose of vitamin C produced effects only in MCF7 cells such as decreased cell viability, modulation of cell cycle re-lated genes, unexpected change in cell phenotype due to estrogen receptor downregulation, catabo-lism of sphingomyelin with a large increase in ceramide. In conclusion, we demonstrated that high doses of VitC on the one hand reduce the growth of lu-minal A type breast cancer cells and on the other hand induce their phenotypic change towards hormone therapy resistant cells. The effect of vitamin C on therapeutic treatment failure of luminal A breast cancer and the possible involvement of high ceramide levels were discussed.

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The ceramide synthase (CERS/LASS) family: Functions involved in cancer progression

Cited by 9 publications

References 116 publications

Untargeted lipidomics reveal association of elevated plasma C18 ceramide levels with reduced survival in metastatic castration-resistant prostate cancer patients

Untargeted lipidomics reveal association of elevated plasma C18 ceramide levels with reduced survival in metastatic castration-resistant prostate cancer patients

FAST: a fast and scalable factor analysis for spatially aware dimension reduction of multi-section spatial transcriptomics data

Vitamin C Modifies the Phenotype of Hormone Receptor Positive/HER2 Negative Breast Cancer Cells and Induces Changes in Sphingolipid Metabolism

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