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The central goal of this work was to identify, by MS, the phospholipidome alterations resulting from the silencing of SCD1 in human GBM cells, in order to implement an innovative therapy to fight GBM cell resistance. With this purpose, RNAi technology was employed, and low serum-containing medium was used to mimic nutrient deficiency conditions, at which SCD1 is overexpressed. Besides the expected increase in the saturated to unsaturated fatty acid ratio in SCD1 silenced-GBM cells, a striking increase in polyunsaturated chains, particularly in phosphatidylethanolamine and cardiolipin species, was noticed and tentatively correlated with an increase in autophagy (evidenced by the increase in LC3BII\/I ratio). The contribution of autophagy to mitigate the impact of SCD1 silencing on GBM cell viability and growth, whose modest inhibition could be correlated with the maintenance of energetically associated mitochondria, was evidenced by using autophagy inhibitors. In conclusion, SCD1 silencing could constitute an important tool to halt GBM resistance to the available treatments, especially when coupled with a mitochondria disrupter chemotherapeutic.<\/jats:p>","DOI":"10.3390\/ijms232113014","type":"journal-article","created":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T20:37:58Z","timestamp":1666903078000},"page":"13014","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Stearoyl CoA Desaturase-1 Silencing in Glioblastoma Cells: Phospholipid Remodeling and Cytotoxicity Enhanced upon Autophagy Inhibition"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4762-0798","authenticated-orcid":false,"given":"Catarina M.","family":"Morais","sequence":"first","affiliation":[{"name":"Department of Life Sciences, University of Coimbra, Cal\u00e7ada Martim de Freitas, 3000-456 Coimbra, Portugal"},{"name":"CNC\u2014Centre for Neuroscience and Cell Biology, CIIB\u2014Centre for Innovative Biomedicine and Biotechnology, IIIUC\u2014Institute for Interdisciplinary Research, University of Coimbra, 3004-504 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1629-4782","authenticated-orcid":false,"given":"Ana M.","family":"Cardoso","sequence":"additional","affiliation":[{"name":"CNC\u2014Centre for Neuroscience and Cell Biology, CIIB\u2014Centre for Innovative Biomedicine and Biotechnology, IIIUC\u2014Institute for Interdisciplinary Research, University of Coimbra, 3004-504 Coimbra, Portugal"}]},{"given":"Ana Rita D.","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Centre, LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Santiago University Campus, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4537-9902","authenticated-orcid":false,"given":"Ana","family":"Reis","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Centre, LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Santiago University Campus, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8060-7675","authenticated-orcid":false,"given":"Pedro","family":"Domingues","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Centre, LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Santiago University Campus, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5357-3601","authenticated-orcid":false,"given":"Maria Ros\u00e1rio M.","family":"Domingues","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Centre, LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Santiago University Campus, 3810-193 Aveiro, Portugal"},{"name":"CESAM\u2014Centre for Environmental and Marine Studies, Department of Chemistry, University of Aveiro, Santiago University Campus, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1844-5027","authenticated-orcid":false,"given":"Maria C. 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