Pivotal role of human stearoyl-CoA desaturases (SCD1 and 5) in breast cancer progression: oleic acid-based effect of SCD1 on cell migration and a novel pro-cell survival role for SCD5
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Cristiana Angelucci1, Alessio D’Alessio1, Fortunata Iacopino1, Gabriella Proietti1, Alba Di Leone2, Riccardo Masetti2 and Gigliola Sica1
1Istituto di Istologia e Embriologia, Università Cattolica del Sacro Cuore, Roma, Italia
2Unità Operativa di Chirurgia Senologica, Università Cattolica Del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli, Roma, Italia
Cristiana Angelucci, email: [email protected]
Keywords: breast cancer cells; cancer-associated fibroblasts; stearoyl-CoA desaturase; cell migration; necrosis
Received: November 13, 2017 Accepted: April 05, 2018 Published: May 11, 2018
The influence of cell membrane fluidity on cancer progression has been established in different solid tumors. We previously reported that “cancer-associated fibroblasts” (CAFs) induced epithelial-mesenchymal transition and increased cell membrane fluidity and migration in poorly (MCF-7) and highly invasive (MDA-MB-231) breast cancer cells. We also found that the membrane fluidity regulating enzyme stearoyl-CoA desaturase 1 (SCD1) was upregulated in tumor cells co-cultured with CAFs and established its essential role for both intrinsic and CAF-driven tumor cell motility. Here, we further explored the mechanisms involved in the SCD1-based modulation of breast cancer cell migration and investigated the role of the other human SCD isoform, SCD5. We showed that the addition of oleic acid, the main SCD1 product, nullified the inhibitory effects produced on MCF-7 and MDA-MB-231 cell migration by SCD1 depletion (pharmacological or siRNA-based). Conversely, SCD5 seemed not involved in the regulation of cancer cell motility. Interestingly, a clear induction of necrosis was observed as a result of the depletion of SCD5 in MCF-7 cells, where the expression of SCD5 was found to be upregulated by CAFs. The necrotic effect was rescued by a 48-h treatment of cells with oleic acid. These results provide further insights in understanding the role of SCD1 in both intrinsic and CAF-stimulated mammary tumor cell migration, unveiling the metabolic basis of this desaturase-triggered effect. Moreover, our data suggest the ability of CAFs to promote the maintenance of tumor cell survival by the induction of SCD5 levels.
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