The Role of Ceramide Metabolism and Signaling in the Regulation of Mitophagy and Cancer Therapy

Sheridan, Megan A.; Öğretmen, Besim

doi:10.3390/cancers13102475

Cited by 61 publications

(40 citation statements)

References 193 publications

(251 reference statements)

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“…In this sense, for cardiovascular (CV) death in individuals with coronary artery disease, the ratios comparing the relative proportion of long-chain ceramides (carbon chain length [14][15][16][17][18] major CV events in healthy individuals or cancer mortality (55,57,58). Following a similar approach as the Mayo Clinic, we focused on the two major species that constitute the main changes observed in our study (Figure 5) and which are consistent with previous works of glioma-related research (52,54). Thus, instead of looking at the trend of each significant individual ceramide, we have found more interesting to determine the relative proportion of C16 Cer in relation to C24:1 Cer in form of a ratio in order to better express a common pattern of the changes observed (Figure 6).…”

Section: Ceramides In Glioblastoma-derived Exosomessupporting

confidence: 85%

“…Recently, the ceramide species ratios were incorporated by the Mayo Clinic as an alternative option to single ceramide values (53); their use is becoming common and being implemented in the clinic (54)(55)(56). In this sense, for cardiovascular (CV) death in individuals with coronary artery disease, the ratios comparing the relative proportion of long-chain ceramides (carbon chain length [14][15][16][17][18] major CV events in healthy individuals or cancer mortality (55,57,58).…”

Section: Ceramides In Glioblastoma-derived Exosomesmentioning

confidence: 99%

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Ceramide Composition in Exosomes for Characterization of Glioblastoma Stem-Like Cell Phenotypes

et al. 2022

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Glioblastoma (GBM) is one of the most malignant central nervous system tumor types. Comparative analysis of GBM tissues has rendered four major molecular subtypes. From them, two molecular subtypes are mainly found in their glioblastoma cancer stem-like cells (GSCs) derived in vitro: proneural (PN) and mesenchymal (MES) with nodular (MES-N) and semi-nodular (MES-SN) disseminations, which exhibit different metabolic, growth, and malignancy properties. Many studies suggest that cancer cells communicate between them, and the surrounding microenvironment, via exosomes. Identifying molecular markers that allow the specific isolation of GSC-derived exosomes is key in the development of new therapies. However, the differential exosome composition produced by main GSCs remains unknown. The aim of this study was to determine ceramide (Cer) composition, one of the critical lipids in both cells and their cell-derived exosomes, from the main three GSC phenotypes using mass spectrometry-based lipidomics. GSCs from human tissue samples and their cell-derived exosomes were measured using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF-MS) in an untargeted analysis. Complete characterization of the ceramide profile, in both cells and cell-derived exosomes from GSC phenotypes, showed differential distributions among them. Results indicate that such differences of ceramide are chain-length dependent. Significant changes for the C16 Cer and C24:1 Cer and their ratio were observed among GSC phenotypes, being different for cells and their cell-derived exosomes.

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Section: Ceramides In Glioblastoma-derived Exosomessupporting

confidence: 85%

Section: Ceramides In Glioblastoma-derived Exosomesmentioning

confidence: 99%

Ceramide Composition in Exosomes for Characterization of Glioblastoma Stem-Like Cell Phenotypes

et al. 2022

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“…Breast cancer aggressiveness and proliferation were attributed to suppression of apoptosis via a Cer-associated pathway [ 49 ]. Synthesis and accumulation of Cer mediate cancer cell death via apoptosis, necroptosis, and autophagy [ 45 , 47 , 77 ].…”

Section: Tumor Immune Evasionmentioning

confidence: 99%

Cell surface sphingomyelin: key role in cancer initiation, progression, and immune evasion

2021

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Cell surface biochemical changes, notably excessive increase in outer leaflet sphingomyelin (SM) content, are important in cancer initiation, growth, and immune evasion. Innumerable reports describe methods to initiate, promote, or enhance immunotherapy of clinically detected cancer, notwithstanding the challenges, if not impossibility, of identification of tumor-specific, or associated antigens, the lack of tumor cell surface membrane expression of major histocompatibility complex (MHC) class I alpha and β2 microglobulin chains, and lack of expression or accessibility of Fas and other natural killer cell immune checkpoint molecules. Conversely, SM synthesis and hydrolysis are increasingly implicated in initiation of carcinogenesis and promotion of metastasis. Surface membrane SM readily forms inter- and intra- molecular hydrogen bond network, which excessive tightness would impair cell-cell contact inhibition, inter- and intra-cellular signals, metabolic pathways, and susceptibility to host immune cells and mediators. The present review aims at clarifying the tumor immune escape mechanisms, which face common immunotherapeutic approaches, and attracting attention to an entirely different, neglected, key aspect of tumorigenesis associated with biochemical changes in the cell surface that lead to failure of contact inhibition, an instrumental tumorigenesis mechanism. Additionally, the review aims to provide evidence for surface membrane SM levels and roles in cells resistance to death, failure to respond to growth suppressor signals, and immune escape, and to suggest possible novel approaches to cancer control and cure.

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“…The various sphingolipids fulfill different roles and may have antagonistic effects. Ceramide regulates cell stress response and inhibits cell growth, as well as promoting apoptosis, cell senescence, and autophagy, in particular mitophagy [ 19 , 20 ]. Several ceramides have been associated with mitochondrial dysfunction, including reduced mitochondrial respiratory chain, increased reactive oxygen species (ROS), and reduced mitochondrial membrane potential [ 16 ].…”

Section: Sphingolipidsmentioning

confidence: 99%

Neurodegenerative Disorders: Spotlight on Sphingolipids

Mandik

Vos

2021

IJMS

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Neurodegenerative diseases are incurable diseases of the nervous system that lead to a progressive loss of brain areas and neuronal subtypes, which is associated with an increase in symptoms that can be linked to the affected brain areas. The key findings that appear in many neurodegenerative diseases are deposits of proteins and the damage of mitochondria, which mainly affect energy production and mitophagy. Several causative gene mutations have been identified in various neurodegenerative diseases; however, a large proportion are considered sporadic. In the last decade, studies linking lipids, and in particular sphingolipids, to neurodegenerative diseases have shown the importance of these sphingolipids in the underlying pathogenesis. Sphingolipids are bioactive lipids consisting of a sphingoid base linked to a fatty acid and a hydrophilic head group. They are involved in various cellular processes, such as cell growth, apoptosis, and autophagy, and are an essential component of the brain. In this review, we will cover key findings that demonstrate the relevance of sphingolipids in neurodegenerative diseases and will focus on neurodegeneration with brain iron accumulation and Parkinson’s disease.

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The Role of Ceramide Metabolism and Signaling in the Regulation of Mitophagy and Cancer Therapy

Cited by 61 publications

References 193 publications

Ceramide Composition in Exosomes for Characterization of Glioblastoma Stem-Like Cell Phenotypes

Ceramide Composition in Exosomes for Characterization of Glioblastoma Stem-Like Cell Phenotypes

Cell surface sphingomyelin: key role in cancer initiation, progression, and immune evasion

Neurodegenerative Disorders: Spotlight on Sphingolipids

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