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<title lang=en>Downregulation of ceramide synthase-6 during epithelial-to-mesenchymal transition reduces plasma membrane fluidity and cancer cell motility</title>
<creator>Edmond, Valérie</creator>
<creator>Dufour, Florent</creator>
<creator>Poiroux, Guillaume</creator>
<creator>Shoji, Kenji</creator>
<creator>Malleter, Marine</creator>
<creator>Fouqué, Amélie</creator>
<creator>Tauzin, Sébastien</creator>
<creator>Rimokh, Ruth</creator>
<creator>Sergent, Odile</creator>
<creator>Penna, Aubin</creator>
<creator>Dupuy, Aude</creator>
<creator>Levade, Thierry</creator>
<creator>Théret, Nathalie</creator>
<creator>Micheau, Olivier</creator>
<creator>Ségui, Bruno</creator>
<creator>Legembre, Patrick</creator>
<contributor>Institut de recherche, santé, environnement et travail [Rennes] (Irset) ; Université d'Angers (UA) - Université des Antilles et de la Guyane (UAG) - Université de Rennes 1 (UR1) - École des Hautes Études en Santé Publique [EHESP] (EHESP) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )</contributor>
<contributor>Lipides - Nutrition - Cancer (U866) (LNC) ; Université de Bourgogne (UB) - Institut National de la Santé et de la Recherche Médicale (INSERM)</contributor>
<contributor>INSERM UMR 1037, CNRS ERL 505294, CRCT (UPS) ; UNIVERSITE TOULOUSE</contributor>
<contributor>Centre de Recherche en Cancérologie de Lyon (CRCL) ; Centre Léon Bérard [Lyon] - Université Claude Bernard Lyon 1 (UCBL) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS)</contributor>
<contributor>Institut des Maladies Métaboliques et Cardiovasculaires (I2MC) ; Université Paul Sabatier - Toulouse 3 (UPS) - Hôpital de Rangueil - Institut National de la Santé et de la Recherche Médicale (INSERM)</contributor>
<description>International audience</description>
<source>ISSN: 0950-9232</source>
<source>EISSN: 1476-5594</source>
<source>Oncogene</source>
<publisher>Nature Publishing Group</publisher>
<identifier>hal-01063558</identifier>
<identifier>https://hal.archives-ouvertes.fr/hal-01063558</identifier>
<identifier>https://hal.archives-ouvertes.fr/hal-01063558/file/Down-regulation%20of%20ceramide_accepted.pdf</identifier>
<source>https://hal.archives-ouvertes.fr/hal-01063558</source>
<source>Oncogene, Nature Publishing Group, 2015, 34, pp.996-1005. 〈10.1038/onc.2014.55〉</source>
<identifier>DOI : 10.1038/onc.2014.55</identifier>
<relation>info:eu-repo/semantics/altIdentifier/doi/10.1038/onc.2014.55</relation>
<identifier>PUBMED : 24632610</identifier>
<relation>info:eu-repo/semantics/altIdentifier/pmid/24632610</relation>
<language>en</language>
<subject>[SDV] Life Sciences [q-bio]</subject>
<type>info:eu-repo/semantics/article</type>
<type>Journal articles</type>
<description lang=en>Epithelial-to-mesenchymal transition (EMT) promotes cell motility, which is important for the metastasis of malignant cells, and blocks CD95-mediated apoptotic signaling triggered by immune cells and chemotherapeutic regimens. CD95L, the cognate ligand of CD95, can be cleaved by metalloproteases and released as a soluble molecule (cl-CD95L). Unlike transmembrane CD95L, cl-CD95L does not induce apoptosis but triggers cell motility. Electron paramagnetic resonance was used to show that EMT and cl-CD95L treatment both led to augmentation of plasma membrane fluidity that was instrumental in inducing cell migration. Compaction of the plasma membrane is modulated, among other factors, by the ratio of certain lipids such as sphingolipids in the membrane. An integrative analysis of gene expression in NCI tumor cell lines revealed that expression of ceramide synthase-6 (CerS6) decreased during EMT. Furthermore, pharmacological and genetic approaches established that modulation of CerS6 expression/activity in cancer cells altered the level of C16-ceramide, which in turn influenced plasma membrane fluidity and cell motility. Therefore, this study identifies CerS6 as a novel EMT-regulated gene that has a pivotal role in the regulation of cell migration.Oncogene advance online publication, 17 March 2014; doi:10.1038/onc.2014.55.</description>
<date>2015-02-19</date>
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