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High-grade serous ovarian cancer (HGSOC) remains an unmet medical challenge. Here, we unravel an unanticipated metabolic heterogeneity in HGSOC. By combining proteomic, metabolomic, and bioergenetic analyses, we identify two molecular subgroups, low- and high-OXPHOS. While low-OXPHOS exhibit a glycolytic metabolism, high-OXPHOS HGSOCs rely on oxidative phosphorylation, supported by glutamine and fatty acid oxidation, and show chronic oxidative stress. We identify an important role for the PML-PGC-1α axis in the metabolic features of high-OXPHOS HGSOC. In high-OXPHOS tumors, chronic oxidative stress promotes aggregation of PML-nuclear bodies, resulting in activation of the transcriptional co-activator PGC-1α. Active PGC-1α increases synthesis of electron transport chain complexes, thereby promoting mitochondrial respiration. Importantly, high-OXPHOS HGSOCs exhibit increased response to conventional chemotherapies, in which increased oxidative stress, PML, and potentially ferroptosis play key functions. Collectively, our data establish a stress-mediated PML-PGC-1α-dependent mechanism that promotes OXPHOS metabolism and chemosensitivity in ovarian cancer.
Pubmed ID: 30244973 RIS Download
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A web-based gene list enrichment analysis tool that provides various types of visualization summaries of collective functions of gene lists. It includes new gene-set libraries, an alternative approach to rank enriched terms, and various interactive visualization approaches to display enrichment results using the JavaScript library, Data Driven Documents (D3). The software can also be embedded into any tool that performs gene list analysis. System-wide profiling of genes and proteins in mammalian cells produce lists of differentially expressed genes / proteins that need to be further analyzed for their collective functions in order to extract new knowledge. Once unbiased lists of genes or proteins are generated from such experiments, these lists are used as input for computing enrichment with existing lists created from prior knowledge organized into gene-set libraries.
View all literature mentionsBioinformatics resource system including web server and web service for functional annotation and enrichment analyses of gene lists. Consists of comprehensive knowledgebase and set of functional analysis tools. Includes gene centered database integrating heterogeneous gene annotation resources to facilitate high throughput gene functional analysis.
View all literature mentionsCollection of data of protein sequence and functional information. Resource for protein sequence and annotation data. Consortium for preservation of the UniProt databases: UniProt Knowledgebase (UniProtKB), UniProt Reference Clusters (UniRef), and UniProt Archive (UniParc), UniProt Proteomes. Collaboration between European Bioinformatics Institute (EMBL-EBI), SIB Swiss Institute of Bioinformatics and Protein Information Resource. Swiss-Prot is a curated subset of UniProtKB.
View all literature mentionsWeb server that summarizes lists of Gene Ontology terms by removing redundant terms and visualizing the remaining ones in scatterplots, interactive graphs, treemaps, or tag clouds. Platform: Online tool
View all literature mentionsSoftware for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsAn Antibody supplier; Dako was purchased by Agilent in 2012 and several years later the websites began to reflect the Dako products as part of the Agilent catalog.
View all literature mentionsCompany provides laboratories worldwide with analytical instruments and supplies, clinical and diagnostic testing services, consumables, applications and expertise in life sciences and applied chemical markets.
View all literature mentionsA software which acquires and processes data sets, primarily through the Xcalibur system.
View all literature mentionsWeb server for statistical, functional and integrative analysis of metabolomics data. Web based tool suite used for metabolomic data processing, normalization, multivariate statistical analysis, and data annotation, biomarker discovery and classification.
View all literature mentionslaboratory mouse with name Swiss nude from MGI.
View all literature mentionsCell line SK-OV-3 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis polyclonal targets Acetylated-Lysine
View all literature mentionsThis monoclonal targets slightly modified β-cytoplasmic actin N-terminal peptide, Ac-Asp-Asp-Asp-Ile-Ala-Ala-Leu-Val-Ile-Asp-Asn-Gly-Ser-Gly-Lys, conjugated to KLH
View all literature mentionsThis monoclonal targets ATP5A
View all literature mentionsThis polyclonal targets PPARGC1A
View all literature mentionsThis monoclonal targets NDUFB8 antibody [20E9DH10C12]
View all literature mentionsThis polyclonal targets Acetylated-Lysine
View all literature mentionsThis monoclonal targets slightly modified β-cytoplasmic actin N-terminal peptide, Ac-Asp-Asp-Asp-Ile-Ala-Ala-Leu-Val-Ile-Asp-Asn-Gly-Ser-Gly-Lys, conjugated to KLH
View all literature mentionsThis monoclonal targets ATP5A
View all literature mentionsThis monoclonal targets NDUFB8 antibody [20E9DH10C12]
View all literature mentionsThis monoclonal targets ATP5A
View all literature mentionsThis polyclonal targets Acetylated-Lysine
View all literature mentionsThis polyclonal targets PPARGC1A
View all literature mentionsThis monoclonal targets slightly modified β-cytoplasmic actin N-terminal peptide, Ac-Asp-Asp-Asp-Ile-Ala-Ala-Leu-Val-Ile-Asp-Asn-Gly-Ser-Gly-Lys, conjugated to KLH
View all literature mentionsThis monoclonal targets NDUFB8 antibody [20E9DH10C12]
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