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Regulated IRE1α-dependent decay (RIDD)-mediated reprograming of lipid metabolism in cancer

Almanza, Aitor ; Mnich, Katarzyna ; Blomme, Arnaud ; Robinson, Claire M ; Rodriguez-Blanco, Giovanny ; Kierszniowska, Sylwia ; McGrath, Eoghan P ; Le Gallo, Matthieu ; Pilalis, Eleftherios ; Swinnen, Johannes V ; Chatziioannou, Aristotelis ; Chevet, Eric ; Gorman, Adrienne M ; Samali, Afshin

Nature communications, 2022-05, Vol.13 (1), p.2493-2493, Article 2493 [Periódico revisado por pares]

England: Nature Publishing Group

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Título:
Regulated IRE1α-dependent decay (RIDD)-mediated reprograming of lipid metabolism in cancer
Autor: Almanza, Aitor ; Mnich, Katarzyna ; Blomme, Arnaud ; Robinson, Claire M ; Rodriguez-Blanco, Giovanny ; Kierszniowska, Sylwia ; McGrath, Eoghan P ; Le Gallo, Matthieu ; Pilalis, Eleftherios ; Swinnen, Johannes V ; Chatziioannou, Aristotelis ; Chevet, Eric ; Gorman, Adrienne M ; Samali, Afshin
Assuntos: Accumulation ; Biochemistry, biophysics & molecular biology ; Biochemistry, Genetics and Molecular Biology (all) ; Biochimie, biophysique & biologie moléculaire ; Biosynthesis ; Breast cancer ; Cancer ; Chemistry (all) ; Constraining ; Decay ; Endoplasmic Reticulum Stress - genetics ; Endoribonucleases ; Endoribonucleases - genetics ; Endoribonucleases - metabolism ; Enzymes ; ERN1 protein, human ; General Biochemistry, Genetics and Molecular Biology ; General Chemistry ; General Physics and Astronomy ; Humans ; Life Sciences ; Lipid metabolism ; Lipid Metabolism - genetics ; Lipids ; Metabolism ; Neoplasms ; Nutrient deficiency ; Physics and Astronomy (all) ; Protein folding ; Protein Serine-Threonine Kinases ; Protein Serine-Threonine Kinases - genetics ; RNA, Messenger ; RNA, Messenger - metabolism ; Sciences du vivant ; Tags ; Transcription Factors ; Transcription Factors - metabolism ; Transcriptomes ; Triglycerides ; X-Box Binding Protein 1 ; X-Box Binding Protein 1 - genetics ; X-Box Binding Protein 1 - metabolism
É parte de: Nature communications, 2022-05, Vol.13 (1), p.2493-2493, Article 2493
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
scopus-id:2-s2.0-85129603587
Descrição: IRE1α is constitutively active in several cancers and can contribute to cancer progression. Activated IRE1α cleaves XBP1 mRNA, a key step in production of the transcription factor XBP1s. In addition, IRE1α cleaves select mRNAs through regulated IRE1α-dependent decay (RIDD). Accumulating evidence implicates IRE1α in the regulation of lipid metabolism. However, the roles of XBP1s and RIDD in this process remain ill-defined. In this study, transcriptome and lipidome profiling of triple negative breast cancer cells subjected to pharmacological inhibition of IRE1α reveals changes in lipid metabolism genes associated with accumulation of triacylglycerols (TAGs). We identify DGAT2 mRNA, encoding the rate-limiting enzyme in TAG biosynthesis, as a RIDD target. Inhibition of IRE1α, leads to DGAT2-dependent accumulation of TAGs in lipid droplets and sensitizes cells to nutritional stress, which is rescued by treatment with the DGAT2 inhibitor PF-06424439. Our results highlight the importance of IRE1α RIDD activity in reprograming cellular lipid metabolism.
Editor: England: Nature Publishing Group
Idioma: Inglês

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Regulated IRE1α-dependent decay (RIDD)-mediated reprograming of lipid metabolism in cancer

Almanza, Aitor ; Mnich, Katarzyna ; Blomme, Arnaud ; Robinson, Claire M ; Rodriguez-Blanco, Giovanny ; Kierszniowska, Sylwia ; McGrath, Eoghan P ; Le Gallo, Matthieu ; Pilalis, Eleftherios ; Swinnen, Johannes V ; Chatziioannou, Aristotelis ; Chevet, Eric ; Gorman, Adrienne M ; Samali, Afshin

England: Nature Publishing Group

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