Comprehensive characterization of complex glycosphingolipids in human pancreatic cancer tissues

Hořejší, Karel; Jin, Chunsheng; Vaňková, Zuzana; Jirásko, Robert; Strouhal, Ondřej; Melichar, Bohuslav; Teneberg, Susann; Holčapek, Michal

doi:10.1016/j.jbc.2023.102923

Cited by 8 publications

(4 citation statements)

References 101 publications

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“…In our study, we observed a slight increase in ceramide levels in TRCs, which may be related to the active metabolism of ceramide due to its role as a substrate for generation of sphingolipids with pro-survival functions. Different from the previous study's results that the increasing GSL [61] and C1P [60] in PDAC contribute to malignant metastasis and tumor progression, the significantly elevated sphingosine was observed in PDAC TRCs. The accumulation of sphingosine was the result of the significantly inhibited salvage pathway with the significantly activated sphingosine generation pathway.…”

Section: Discussioncontrasting

confidence: 99%

“…Although cellular stress can induce the accumulation of ceramide and mediate cancer cell death [57], the active metabolism of ceramide has been confirmed in various tumors [58,59]. Ceramide can be converted to ceride-1-phosphate (C1P) [60] and SM [58], respectively, and is also utilized as a precursor for the generation of glycosphingolipids (GSL) including glucosylceramide and lactosylceramide [61]. Ceramide is hydroxylated by ceramidases (CDases) to yield sphingosine, which is phonologically late, by SPHK1 (also known as SK1) or SPHK2 (also known as SK2) to generate S1P [62].…”

Section: Discussionmentioning

confidence: 99%

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Transcriptome and Lipidomic Analysis Suggests Lipid Metabolism Reprogramming and Upregulating SPHK1 Promotes Stemness in Pancreatic Ductal Adenocarcinoma Stem-like Cells

Xu,

Zhou,

et al. 2023

Metabolites

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Cancer stem cells (CSCs) are considered to play a key role in the development and progression of pancreatic ductal adenocarcinoma (PDAC). However, little is known about lipid metabolism reprogramming in PDAC CSCs. Here, we assigned stemness indices, which were used to describe and quantify CSCs, to every patient from the Cancer Genome Atlas (TCGA-PAAD) database and observed differences in lipid metabolism between patients with high and low stemness indices. Then, tumor-repopulating cells (TRCs) cultured in soft 3D (three-dimensional) fibrin gels were demonstrated to be an available PDAC cancer stem-like cell (CSLCs) model. Comprehensive transcriptome and lipidomic analysis results suggested that fatty acid metabolism, glycerophospholipid metabolism, and, especially, the sphingolipid metabolism pathway were mostly associated with CSLCs properties. SPHK1 (sphingosine kinases 1), one of the genes involved in sphingolipid metabolism and encoding the key enzyme to catalyze sphingosine to generate S1P (sphingosine-1-phosphate), was identified to be the key gene in promoting the stemness of PDAC. In summary, we explored the characteristics of lipid metabolism both in patients with high stemness indices and in novel CSLCs models, and unraveled a molecular mechanism via which sphingolipid metabolism maintained tumor stemness. These findings may contribute to the development of a strategy for targeting lipid metabolism to inhibit CSCs in PDAC treatment.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Transcriptome and Lipidomic Analysis Suggests Lipid Metabolism Reprogramming and Upregulating SPHK1 Promotes Stemness in Pancreatic Ductal Adenocarcinoma Stem-like Cells

Xu,

Zhou,

et al. 2023

Metabolites

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“…A previous mass spectrometry-based lipidomics study quantified the changes in sphingolipid-like lipids in pancreatic tumors and plasma specimens and reported that sphingolipid metabolism was altered in human pancreatic cancer and correlated with the advanced stage of the tumor [ 46 ]. A recently reported study systematically analyzed glycosphingolipids isolated from pancreatic cancer tissues, which revealed differences in the profiles and relative amounts of neutral glycosphingolipids between normal and tumor tissues [ 47 ]. Additionally, it has been demonstrated that sphingolipids are engaged in the regulation of tumorigenesis and metastasis in pancreatic cancer [ 12 , 48 ].…”

Section: Discussionmentioning

confidence: 99%

A novel sphingolipid metabolism-related long noncoding RNA signature predicts the prognosis, immune landscape and therapeutic response in pancreatic adenocarcinoma

He,

Xu,

Ren

et al. 2024

Heliyon

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“…By regulating the levels of sphingolipids on cell membranes, it is possible to either increase or decrease the resistance of tumor cells to these drugs (Chiu et al, 2022). Recent studies have shown a significant correlation between some sphingolipid cohort members and the development of PAAD, providing predictive information about the course of the illness (Horejsi et al, 2023;Wilson et al, 2023). Despite the well-established importance of sphingolipids in the field of PAAD, there has been a noticeable lack of thorough investigations into the latent predictive value held by the SPGs, or short for sphingolipid orchestration genes, genes.…”

Section: Introductionmentioning

confidence: 99%

Machine learning-enhanced insights into sphingolipid-based prognostication: revealing the immunological landscape and predictive proficiency for immunomotherapy and chemotherapy responses in pancreatic carcinoma

Shi,

Li,

2023

Front. Mol. Biosci.

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Background: With a poor prognosis for affected individuals, pancreatic adenocarcinoma (PAAD) is known as a complicated and diverse illness. Immunocytes have become essential elements in the development of PAAD. Notably, sphingolipid metabolism has a dual function in the development of tumors and the invasion of the immune system. Despite these implications, research on the predictive ability of sphingolipid variables for PAAD prognosis is strikingly lacking, and it is yet unclear how they can affect PAAD immunotherapy and targeted pharmacotherapy.Methods: The investigation process included SPG detection while also being pertinent to the prognosis for PAAD. Both the analytical capability of CIBERSORT and the prognostic capability of the pRRophetic R package were used to evaluate the immunological environments of the various HCC subtypes. In addition, CCK-8 experiments on PAAD cell lines were carried out to confirm the accuracy of drug sensitivity estimates. The results of these trials, which also evaluated cell survival and migratory patterns, confirmed the usefulness of sphingolipid-associated genes (SPGs).Results: As a result of this thorough investigation, 32 SPGs were identified, each of which had a measurable influence on the dynamics of overall survival. This collection of genes served as the conceptual framework for the development of a prognostic model, which was carefully assembled from 10 chosen genes. It should be noted that this grouping of patients into cohorts with high and low risk was a sign of different immune profiles and therapy responses. The increased abundance of SPGs was identified as a possible sign of inadequate responses to immune-based treatment approaches. The careful CCK-8 testing carried out on PAAD cell lines was of the highest importance for providing clear confirmation of drug sensitivity estimates.Conclusion: The significance of Sphingolipid metabolism in the complex web of PAAD development is brought home by this study. The novel risk model, built on the complexity of sphingolipid-associated genes, advances our understanding of PAAD and offers doctors a powerful tool for developing personalised treatment plans that are specifically suited to the unique characteristics of each patient.

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Comprehensive characterization of complex glycosphingolipids in human pancreatic cancer tissues

Cited by 8 publications

References 101 publications

Transcriptome and Lipidomic Analysis Suggests Lipid Metabolism Reprogramming and Upregulating SPHK1 Promotes Stemness in Pancreatic Ductal Adenocarcinoma Stem-like Cells

Transcriptome and Lipidomic Analysis Suggests Lipid Metabolism Reprogramming and Upregulating SPHK1 Promotes Stemness in Pancreatic Ductal Adenocarcinoma Stem-like Cells

A novel sphingolipid metabolism-related long noncoding RNA signature predicts the prognosis, immune landscape and therapeutic response in pancreatic adenocarcinoma

Machine learning-enhanced insights into sphingolipid-based prognostication: revealing the immunological landscape and predictive proficiency for immunomotherapy and chemotherapy responses in pancreatic carcinoma

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