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

Oncotarget
Cristiana AngelucciGigliola Sica

Abstract

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...Continue Reading

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Citations

Jan 30, 2020·Breast Cancer : the Journal of the Japanese Breast Cancer Society·Marine LingrandCatherine Mounier
Jul 10, 2019·Cancers·Zuzanna Tracz-Gaszewska, Pawel Dobrzyn
Jul 17, 2020·Computational and Mathematical Methods in Medicine·Xinhua XuRongbiao Ying
Jun 13, 2020·International Journal of Molecular Sciences·Bianka BojkováMagdalena Wszedybyl-Winklewska
Jan 9, 2021·Cancer & Metabolism·Shilpa R NagarajanAndrew J Hoy
Apr 4, 2021·International Journal of Environmental Research and Public Health·Pasquale SimeoneAnna M Giudetti
Oct 14, 2020·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·R Ariel Igal, Débora I Sinner
Dec 11, 2021·Frontiers in Cell and Developmental Biology·Marta BiondoBarbara Pergolizzi

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Methods Mentioned

BETA
transfection
nuclear translocation
PCR

Software Mentioned

Quantity One
Chemi Doc Documentation System
ImageJ
ISCapture

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