Fatty acid synthase as a feasible biomarker for triple negative breast cancer stem cell subpopulation cultured on electrospun scaffolds
| Author(s) | Rabionet, Marc | |
| Author(s) | Polonio-Alcalá, Emma | |
| Author(s) | Relat, Joana | |
| Author(s) | Yeste, Marc | |
| Author(s) | Sims-Mourtada, Jennifer | |
| Author(s) | Kloxin, April M. | |
| Author(s) | Planas, Marta | |
| Author(s) | Feliu, Lidia | |
| Author(s) | Ciurana, Joaquim | |
| Author(s) | Puig, Teresa | |
| Date Accessioned | 2023-10-11T17:11:14Z | |
| Date Available | 2023-10-11T17:11:14Z | |
| Publication Date | 2021-09 | |
| Description | This article was originally published in Materials Today Bio. The version of record is available at: https://doi.org/10.1016/j.mtbio.2021.100155. © 2021 Published by Elsevier Ltd. | |
| Abstract | There is no targeted therapy for triple negative breast cancer (TNBC), which presents an aggressive profile and poor prognosis. Recent studies noticed the feasibility of breast cancer stem cells (BCSCs), a small population responsible for tumor initiation and relapse, to become a novel target for TNBC treatments. However, new cell culture supports need to be standardized since traditional two-dimensional (2D) surfaces do not maintain the stemness state of cells. Hence, three-dimensional (3D) scaffolds represent an alternative to study in vitro cell behavior without inducing cell differentiation. In this work, electrospun polycaprolactone scaffolds were used to enrich BCSC subpopulation of MDA-MB-231 and MDA-MB-468 TNBC cells, confirmed by the upregulation of several stemness markers and the existence of an epithelial-to-mesenchymal transition within 3D culture. Moreover, 3D-cultured cells displayed a shift from MAPK to PI3K/AKT/mTOR signaling pathways, accompanied by an enhanced EGFR and HER2 activation, especially at early cell culture times. Lastly, the fatty acid synthase (FASN), a lipogenic enzyme overexpressed in several carcinomas, was found to be hyperactivated in stemness-enriched samples. Its pharmacological inhibition led to stemness diminishment, overcoming the BCSC expansion achieved in 3D culture. Therefore, FASN may represent a novel target for BCSC niche in TNBC samples. Highlights • Polycaprolactone scaffolds provide a softer 3D alternative to traditional cell culture. • Scaffolds expand the triple negative breast cancer stem cell niche. • Fatty Acid Synthase (FASN) is hyperactivated in scaffold-cultured cells. • FASN inhibition overcomes the stemness expansion achieved in 3D culture. Graphical abstract available at: https://doi.org/10.1016/j.mtbio.2021.100155 | |
| Sponsor | This work was supported by Spanish grants from Fundación Ramón Areces, Instituto de Salud Carlos III and co-funded by European Union (ERDF/ESF, “A way to make Europe”/”Investing in your future”) (PI19/00372), and Ministerio de Economía y Competitividad (DPI2016-77156-R). The authors are grateful to Marc Rabionet pre-doctoral grant (IFUdG2017/62), Emma Polonio-Alcalá pre-doctoral grant (2019FI_B01011), the support of the Catalan Government (2017SGR00385), and Oncolliga Foundation and RadikalSwim (OncoSwim). The authors thank the researcher Sabina Couto-Ovejero and the Research Technical Services from the University of Girona. The authors are also grateful to Lynn Opdenaker and the flow cytometry core at the Cawley Center for Translational Research, Helen F Graham Cancer Center, which is supported by the Delaware INBRE program, with a grant from the National Institute of General Medical Sciences – NIGMS (P20 GM103446) from the National Institutes of Health and the State of Delaware. | |
| Citation | Rabionet, Marc, Emma Polonio-Alcalá, Joana Relat, Marc Yeste, Jennifer Sims-Mourtada, April M. Kloxin, Marta Planas, Lidia Feliu, Joaquim Ciurana, and Teresa Puig. “Fatty Acid Synthase as a Feasible Biomarker for Triple Negative Breast Cancer Stem Cell Subpopulation Cultured on Electrospun Scaffolds.” Materials Today Bio 12 (September 1, 2021): 100155. https://doi.org/10.1016/j.mtbio.2021.100155. | |
| ISSN | 2590-0064 | |
| URL | https://udspace.udel.edu/handle/19716/33532 | |
| Publisher | Materials Today Bio | |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
| Keywords | triple negative breast cancer | |
| Keywords | three-dimensional cell culture | |
| Keywords | polycaprolactone | |
| Keywords | electrospun scaffolds | |
| Keywords | breast cancer stem cells | |
| Keywords | fatty acid synthase | |
| Keywords | good health and well-being | |
| Title | Fatty acid synthase as a feasible biomarker for triple negative breast cancer stem cell subpopulation cultured on electrospun scaffolds | |
| Type | Article |
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