Dataset Information

MDM2-Dependent Rewiring of Metabolomic and Lipidomic Profiles in Dedifferentiated Liposarcoma Models

ABSTRACT: Dedifferentiated liposarcoma (DDLPS) is an aggressive mesenchymal cancer marked by amplification of MDM2, an inhibitor of the tumor suppressor TP53. DDLPS patients with higher MDM2 amplification have lower chemotherapy sensitivity and worse outcome than patients with lower MDM2 amplification. We hypothesized that MDM2 amplification levels may be associated with changes in DDLPS metabolism. Six patient-derived DDLPS cell line models were subject to comprehensive metabolomic (Metabolon) and lipidomic (SCIEX 5600 TripleTOF-MS) profiling to assess associations with MDM2 amplification and their responses to metabolic perturbations. Comparing metabolomic profiles between MDM2 higher and lower amplification cells yielded a total of 23 differentially abundant metabolites across both panels (FDR < 0.05, log2 FC < 0.75), including ceramides, glycosylated ceramides, and sphingomyelins. Disruption of lipid metabolism through statin administration resulted in a chemo-sensitive phenotype in MDM2 lower cell lines only, suggesting that lipid metabolism may be a large contributor to the more aggressive nature of MDM2 higher DDLPS tumors. This study is the first to provide comprehensive metabolomic and lipidomic characterization of DDLPS cell lines and provides evidence for MDM2-dependent differential molecular mechanisms that are critical factors in chemoresistance and could thus affect patient outcome.

ORGANISM(S): Human Homo Sapiens

TISSUE(S): Cultured Cells

SUBMITTER: Andrew Patt

PROVIDER: ST001405 | MetabolomicsWorkbench | Fri May 22 00:00:00 BST 2020

REPOSITORIES: MetabolomicsWorkbench

ACCESS DATA

Similar Datasets

Project description:Tocopherols (vitamin E) are lipid-soluble antioxidants produced by all plants and algae, and many cyanobacteria, yet their functions in these photosynthetic organisms are still not fully understood. We have previously reported that the vitamin E deficient 2 (vte2) mutant of Arabidopsis thaliana is sensitive to low temperature (LT) due to impaired transfer cell wall (TCW) development and photoassimilate export, associated with massive callose deposition in transfer cells of the phloem. To further understand the roles of tocopherols in LT induced TCW development we compared the global transcript profiles of vte2 and wild type leaves during LT treatment. Tocopherol deficiency had no significant impact on global gene expression in permissive conditions, but significantly affected expression of 77 genes after 48 hours of LT treatment. In vte2 relative to wild type, genes associated with solute transport were repressed, while those involved in various pathogen responses and cell wall modifications, such as GLUCAN SYNTHASE LIKE genes (GSL4 and GSL11), were induced. The vte2 LT experiment comprised 18 chips in a factorial design. vte2 and Col plants were grown under permisive conditions for four weeks, Three independent biological replicates were conducted for Col and vte2 at each of the three time points during LT treatment. 0h represent when they are physiologically and biochemically indistinguishable, and at two time points of LT treatment (48 h, 120 h) selected based on our previous timecourse study of the physiological and biochemical changes of vte2 and Col during LT treatment (Maeda et al., 2006). After 48 h of LT, vascular callose deposition is strongly induced and photoassimilate export capacity is significantly lower in vte2 compared to Col, though the visible whole plant phenotypes and soluble sugar accumulation between the two genotypes do not differ (Maeda et al., 2006). The 120 h LT timepoint represents a relatively late response of vte2 when soluble sugars are significantly higher and callose deposition is even more extensive and wide spread in vte2 (Maeda et al., 2006). Thus the 48 h time point should allow identification of early responses to tocopherol deficiency that are distinct from later, pleiotropic responses resulting from the strongly elevated sugar levels in vte2 after 120 h of LT. The 0 h time point represents the absence of LT treatment (see method) and serves as a critical treatment control. 7°C. Three biological replicated the 9 to 11th oldest rosetta leaves from three independent plants were harvested together into a tube filled with liquid nitrogen one hour into the light cycle after 48 and 120 hours of LT-treatment or without LT-treatment (referred to as 0 hour LT treatment).

Dataset Information

MDM2-Dependent Rewiring of Metabolomic and Lipidomic Profiles in Dedifferentiated Liposarcoma Models

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure