KOPS - The Institutional Repository of the University of Konstanz

p53-driven lipidome influences non-cell-autonomous lysophospholipids in pancreatic cancer

p53-driven lipidome influences non-cell-autonomous lysophospholipids in pancreatic cancer

Cite This

Files in this item

Checksum: MD5:f20741500fff68cd9a4a1dd5512afe06

BUTERA, Alessio, Micaela ROY, Carlotta ZAMPIERI, Eleonora MAMMARELLA, Emanuele PANATTA, Gerry MELINO, Angelo D'ALESSANDRO, Ivano AMELIO, 2022. p53-driven lipidome influences non-cell-autonomous lysophospholipids in pancreatic cancer. In: Biology direct. BioMed Central. 17(1), 6. eISSN 1745-6150. Available under: doi: 10.1186/s13062-022-00319-9

@article{Butera2022p53dr-57166, title={p53-driven lipidome influences non-cell-autonomous lysophospholipids in pancreatic cancer}, year={2022}, doi={10.1186/s13062-022-00319-9}, number={1}, volume={17}, journal={Biology direct}, author={Butera, Alessio and Roy, Micaela and Zampieri, Carlotta and Mammarella, Eleonora and Panatta, Emanuele and Melino, Gerry and D'Alessandro, Angelo and Amelio, Ivano}, note={Article Number: 6} }

<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#" xmlns:foaf="http://xmlns.com/foaf/0.1/" xmlns:void="http://rdfs.org/ns/void#" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/rdf/resource/123456789/57166"> <dcterms:abstract xml:lang="eng">Adaptation of the lipid metabolism participates  in cancer pathogenesis, facilitating energy storage and influencing cell fate and control of molecular signalling. The tumour suppressor protein p53 is a molecular hub of cell metabolism, supporting antioxidant capabilities and counteracting oncogene-induced metabolic switch. Despite extensive work has described the p53-dependent metabolic pathways, a global profiling of p53 lipidome is still missing. By high-throughput untargeted lipidomic analysis of pancreatic ductal adenocarcinoma (PDAC) cells, we profile the p53-dependent lipidome, revealing intracellular and secreted lysophospholipids as one of the most affected class. Lysophospholipids are hydrolysed forms of phospholipids that results from phospholipase activity, which can function as signalling molecules, exerting non-cell-autonomous effects and instructing cancer microenvironment and immunity. Here, we reveal that p53 depletion reduces abundance of intracellular lysophosphatidyl-choline, -ethanolamine and -serine and their secretion in the extracellular environment. By integrating this with genomic and transcriptomic studies from in vitro models and human PDAC patients, we identified potential clinically relevant candidate p53-dependent phospholipases. In particular PLD3, PLCB4 and PLCD4 expression is regulated by p53 and chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) indicates a direct transcriptional control on their chromatin accessible genomic loci. Consistently, PLD3, PLCB4 and PLCD4 expression correlates with p53 mutational status in PDAC patients, and these genes display prognostic significance. Overall, our data provide insights into lipidome rewiring driven by p53 loss and identify alterations of lysophospholipids as a potential molecular mechanism for p53-mediated non-cell-autonomous molecular signalling that instructs cancer microenvironment and immunity during PDAC pathogenesis.</dcterms:abstract> <dc:contributor>Amelio, Ivano</dc:contributor> <dc:creator>Melino, Gerry</dc:creator> <dc:contributor>Melino, Gerry</dc:contributor> <dc:creator>Butera, Alessio</dc:creator> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> <dc:contributor>D'Alessandro, Angelo</dc:contributor> <dc:contributor>Roy, Micaela</dc:contributor> <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/57166"/> <dc:rights>Attribution 4.0 International</dc:rights> <dcterms:issued>2022</dcterms:issued> <dc:contributor>Zampieri, Carlotta</dc:contributor> <dc:contributor>Panatta, Emanuele</dc:contributor> <dc:contributor>Mammarella, Eleonora</dc:contributor> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2022-04-05T08:53:21Z</dcterms:available> <dc:creator>Panatta, Emanuele</dc:creator> <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/57166/1/Butera_2-19003t3t7kwot5.pdf"/> <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <dc:creator>Zampieri, Carlotta</dc:creator> <dcterms:rights rdf:resource="http://creativecommons.org/licenses/by/4.0/"/> <dc:creator>Amelio, Ivano</dc:creator> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2022-04-05T08:53:21Z</dc:date> <foaf:homepage rdf:resource="http://localhost:8080/jspui"/> <dc:language>eng</dc:language> <dc:creator>Roy, Micaela</dc:creator> <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/57166/1/Butera_2-19003t3t7kwot5.pdf"/> <dcterms:title>p53-driven lipidome influences non-cell-autonomous lysophospholipids in pancreatic cancer</dcterms:title> <dc:contributor>Butera, Alessio</dc:contributor> <dc:creator>D'Alessandro, Angelo</dc:creator> <dc:creator>Mammarella, Eleonora</dc:creator> </rdf:Description> </rdf:RDF>

Downloads since Apr 5, 2022 (Information about access statistics)

Butera_2-19003t3t7kwot5.pdf 115

This item appears in the following Collection(s)

Attribution 4.0 International Except where otherwise noted, this item's license is described as Attribution 4.0 International

Search KOPS


Browse

My Account