Transcriptomic analysis of effects of cancer cell detachment after treatment with 2-deoxy-D-glucose alone or in co-treatment with metformin
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE279580 | GEO | 2024/10/20
REPOSITORIES: GEO
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Project description:2-deoxy-D-glucose (2DG) is a glucose analog that is established to inhibit glucose metabolism via glycolysis. It has long been recognized as a potential chemical mimetic of calorie restriction, and it also has been shown to have anti-viral effects in infected cells, against among others SARS-CoV-2. This study aimed to determine whether intermittent treatment of mice with 2DG could alter nutrient metabolism in vivo and whether this would produce a proteomic signature of altered glucose metabolism and other cellular pathways, with a view to explaining the anti-viral properties of 2DG. Parallel physiological studies of the heart aimed to relate any proteomic changes to the function and performance of the heart, including assessing whether there were any signs of detrimental effects of 2DG.
2022-05-20 | PXD027974 | Pride
Project description:Transcriptomic analysis of effects of cancer cell detachment after treatment with 2-deoxy-D-glucose alone or in co-treatment with metformin
| PRJNA1173549 | ENA
Project description:The Warburg effect, consisting of increased glucose uptake and glycolysis, provides metabolic energy as well as cellular building blocks for tumor growth. Inhibition of the Warburg effect with 2-deoxyglucose (2DG) has been explored in clinical trials with limited efficacy. Blockage of glycolysis can induce autopahgy resulting in alternative energy generation through oxidative phosphorylation providing a potential bypass of the effects of inhibition of glycolysis. Here in we demonstrate that activation of AMPK, as a consequence of energetic stress, induces mitochondrial energy production potentially bypassing the effects of glycolysis inhibition. We thus combined blockage of glycolysis by 2DG with inhibition of the electron transfer complex I (ETC1) in the mitochondria with the clinically applicable antidiabetic drug metformin. The combination resulted in activation of AMPK and autopahgy that however rendered eventual depletion of ATP and cell death. Furthermore, combined inhibition of glycolysis and mitochondrial respiration inhibited tumor growth and markedly decreased metastatic capacity in vivo. In order to understand the mechanism of these metabolic inhibitors, we performed whole genome transcriptional analysis. Human SK-4 esophageal cancer cell lines were treated with 5 different treatment groups [2 deoxy glucose (4mM), Metformin (5mM), AICAR (2mM), 2 deoxy glucose (4mM) plus Metformin (5mM) and 2 deoxy glucose (4mM) plus AICAR (2mM)] with non treated control groups for 12 hrs. Each groups was quadruplicated. Microarray experiments and data analysis were done at Dept. of Systems Biology, MDACC (Houston, USA)
2012-12-31 | E-GEOD-16816 | biostudies-arrayexpress
Project description:Spautin-1 as well as buformin showed preferential cytotoxicity under 2-deoxy-D-glucose (2DG)-stressed, but not tunicamycin-stressed conditions in HT-29 cells. By a microarray-based transcription analyses, we previously identified an unfolded protein response (UPR) expression signature, consisting of 246 probes up- or down-regulated in glucose starvation- and 2DG-stressed HT-29 and other cancer cell lines. Thus, we compared the effects of spautin-1 and buformin on the UPR transcriptional program. The two UPR inhibitors partly canceled 2DG-induced, but not TM-induced changes in UPR expression signature, indicating that spautin-1 can indeed suppress the UPR transcriptional program under 2DG-stressed conditions.
2022-07-07 | GSE189850 | GEO
Project description:Epidermis, a continuously self-renewing and differentiating organ, produces a protective stratum corneum that shields us from external chemical, physical and microbial threats. Epidermal differentiation is a multi-step process regulated by influences, some unknown, others insufficiently explored. Detachment of keratinocytes from the basement membrane is one such pro-differentiation stimulus. Here, we define the transcriptional changes during differentiation, especially those caused by detachment from the substratum. Using comprehensive transcriptional profiling, we revisited the effects of detachment as a differentiation signal to keratinocytes. We identified the genes regulated by detachment, the corresponding ontological categories and, using metaanalysis, compared the genes and categories to those regulated by other pro-differentiating stimuli. We identified 762 genes overexpressed in suspended keratinocyte, including known and novel differentiation markers, and 1427 in attached cells, including basal layer markers. Detachment induced epidermis development, cornification and desmosomal genes, but also innate immunity, proliferation inhibitors, transcription regulators and MAPKs; conversely the attached cells overexpressed cell cycle, anchoring, motility, splicing and mitochondrial genes, and both positive and negative regulators of apoptosis. Metaanalysis identified which detachment-regulated categories overlap with those induced by suprabasal location in vivo, by reaching confluency in vitro, and by inhibition of JUN kinases. Attached and in vivo basal cells shared overexpression of mitochondrial components. Interestingly, melanosome trafficking components were also overexpressed in the attached and in vivo basal keratinocytes. Reaching confluency did not affect adhesion and ECM proteins. Lipid metabolism and steroid metabolism were induced by confluency and by JNK inhibition, respectively. These results suggest that specific pro-differentiation signals induce specific features of the keratinization process, which are in vivo orchestrated into harmonious epidermal homeostasis. Human epidermal keratinocytes are grown in standard growth medium either attached in tissue culture plates, or suspended, in the same medium, in bacteriological plates. After 48 hrs, attached and suspended cultures were harvested and their transcriptomes compared.
2014-04-25 | E-GEOD-57045 | biostudies-arrayexpress
Project description:Glycolytic inhibition via 2-deoxy-D-glucose (2DG) has potential therapeutic benefits for a range of diseases, including cancer, epilepsy, systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA), and COVID-19, but the systemic effects of 2DG on gene function across different tissues are unclear. This study analyzed the transcriptional profiles of nine tissues from C57BL/6J mice treated with 2DG to understand how it modulates pathways systemically. Principal component analysis (PCA), weighted gene co-network analysis (WGCNA), analysis of variance, and pathway analysis were all performed to identify modules altered by 2DG treatment. Data analyses, data, and code are available as a data resource website. PCA revealed that samples clustered predominantly by tissue, suggesting that 2DG affects each tissue uniquely. Unsupervised clustering and WGCNA revealed six distinct tissue-specific modules significantly affected by 2DG, each with unique key pathways and genes. 2DG predominantly affected mitochondrial metabolism in the heart, while in the small intestine, it affected immunological pathways. These findings suggest that 2DG has a systemic impact that varies across organs, potentially affecting multiple pathways and functions. The study provides insights into the potential therapeutic benefits of 2DG across different diseases and highlights the importance of understanding its systemic effects for future research and clinical applications.
2024-11-18 | GSE248967 | GEO
Project description:Epidermis, a continuously self-renewing and differentiating organ, produces a protective stratum corneum that shields us from external chemical, physical and microbial threats. Epidermal differentiation is a multi-step process regulated by influences, some unknown, others insufficiently explored. Detachment of keratinocytes from the basement membrane is one such pro-differentiation stimulus. Here, we define the transcriptional changes during differentiation, especially those caused by detachment from the substratum. Using comprehensive transcriptional profiling, we revisited the effects of detachment as a differentiation signal to keratinocytes. We identified the genes regulated by detachment, the corresponding ontological categories and, using metaanalysis, compared the genes and categories to those regulated by other pro-differentiating stimuli. We identified 762 genes overexpressed in suspended keratinocyte, including known and novel differentiation markers, and 1427 in attached cells, including basal layer markers. Detachment induced epidermis development, cornification and desmosomal genes, but also innate immunity, proliferation inhibitors, transcription regulators and MAPKs; conversely the attached cells overexpressed cell cycle, anchoring, motility, splicing and mitochondrial genes, and both positive and negative regulators of apoptosis. Metaanalysis identified which detachment-regulated categories overlap with those induced by suprabasal location in vivo, by reaching confluency in vitro, and by inhibition of JUN kinases. Attached and in vivo basal cells shared overexpression of mitochondrial components. Interestingly, melanosome trafficking components were also overexpressed in the attached and in vivo basal keratinocytes. Reaching confluency did not affect adhesion and ECM proteins. Lipid metabolism and steroid metabolism were induced by confluency and by JNK inhibition, respectively. These results suggest that specific pro-differentiation signals induce specific features of the keratinization process, which are in vivo orchestrated into harmonious epidermal homeostasis.
2014-04-25 | GSE57045 | GEO
Project description:Inhibiting the unfolded protein response (UPR) can be a therapeutic approach, especially for targeting the tumor microenvironment. We found that compound C (also known as dorsomorphin) prevented the UPR and exerted enhanced cytotoxicity during glucose deprivation. The UPR-inhibiting activity of compound C was not associated with either AMPK or BMP signaling inhibition. To induce the UPR, we treated HT1080 cells for 18 hours under ER stress conditions by adding 10 mM 2-Deoxy-D-glucose (2DG) to culture medium. UPR inhibitors (compound C, versipelostatin and phenformin) were added just before 2DG was added in medium. Total 8 samples were prepared for RNA extraction and hybridization on Affymetrix microarrays.
2012-10-11 | E-GEOD-32911 | biostudies-arrayexpress
Project description:A zebra mussel byssus cDNA microarray was used to identify the differentially expressed genes between attachment and detachment. Keywords: Gene differential expression The zebra mussels were divided in to two groups: AT and DT. In group AT all the zebra mussels were kept in the water attached for 48 hours while in group DT, the individuals were kept detached underwater for 48 hours. The feet of the zebra mussels were taken from each group. Four replicates, including four individual feet each replicate, were taken from each group for total RNA extraction. Four microarray hybridization performed between AT and DE. In each group, two cDNA replicates were labeled with Alexa 555 while the other two were labeled with Alexa 647. Every hybridization happened between two cDNA samples from different group with different labels.
2008-04-19 | E-GEOD-10851 | biostudies-arrayexpress
Project description:Metastasis of cancer cells requires detachment from Extra Cellular Matrix (ECM) to seed cancer cells in a distant organ. Hypoxia is prevalent in this matrix detached cancer cells. Studies have established hypoxia as a chromatin modifier, as it transcriptionally controls expression of various histone demethylases (KDMs); therefore, we hypothesized that the presence of hypoxia could modulate the expression of KDMs in matrix detached cancer cells. Our study showed that in matrix detached cancer cells, both hypoxia and one of the hypoxia regulated H3K27me3 histone demethylase, namely KDM6B, was increased. Simultaneously, we found increased expression of stemness-associated genes, namely SOX-2, SOX-9, and CD44, in hypoxic matrix detached cancer cells. We discovered that KDM6B occupies the promoter region of both SOX-2 and CD44 to regulate their expression epigenetically. Targeting KDM6B reduces its occupancy, thereby expressing the stemness-related genes in matrix detached cancer cells. Further, we noticed increased occupancy of HIF1α promoter by KDM6B, suggesting its regulatory role in maintaining hypoxia in matrix detached cancer cells. This observation was further strengthened as we found a significant positive association between KDM6B and HIF1α in various cancer types. Overall, we found that matrix detachment modulates epigenome by inducing KDM6B activity to regulate the expression of stemness-related genes and hypoxia primarily through HIF1α in matrix detached conditions. KDM6B can be developed as a therapeutic target to eliminate matrix detached cancer cells bound for metastatic events
2021-06-11 | GSE176558 | GEO