Fatty acid synthase as a feasible biomarker for triple negative breast cancer stem cell subpopulation cultured on electrospun scaffolds

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 TN...

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Autores principales:	Marc Rabionet, Emma Polonio-Alcalá, Joana Relat, Marc Yeste, Jennifer Sims-Mourtada, April M. Kloxin, Marta Planas, Lidia Feliu, Joaquim Ciurana, Teresa Puig
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Triple negative breast cancer Three-dimensional cell culture Polycaprolactone Electrospun scaffolds Breast cancer stem cells Fatty acid synthase Medicine (General) R5-920 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/802999fcfc304b2a82c214d992ee0995
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spelling	oai:doaj.org-article:802999fcfc304b2a82c214d992ee09952021-11-20T05:12:43ZFatty acid synthase as a feasible biomarker for triple negative breast cancer stem cell subpopulation cultured on electrospun scaffolds2590-006410.1016/j.mtbio.2021.100155https://doaj.org/article/802999fcfc304b2a82c214d992ee09952021-09-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2590006421000636https://doaj.org/toc/2590-0064There 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.Marc RabionetEmma Polonio-AlcaláJoana RelatMarc YesteJennifer Sims-MourtadaApril M. KloxinMarta PlanasLidia FeliuJoaquim CiuranaTeresa PuigElsevierarticleTriple negative breast cancerThree-dimensional cell culturePolycaprolactoneElectrospun scaffoldsBreast cancer stem cellsFatty acid synthaseMedicine (General)R5-920Biology (General)QH301-705.5ENMaterials Today Bio, Vol 12, Iss , Pp 100155- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Triple negative breast cancer Three-dimensional cell culture Polycaprolactone Electrospun scaffolds Breast cancer stem cells Fatty acid synthase Medicine (General) R5-920 Biology (General) QH301-705.5
spellingShingle	Triple negative breast cancer Three-dimensional cell culture Polycaprolactone Electrospun scaffolds Breast cancer stem cells Fatty acid synthase Medicine (General) R5-920 Biology (General) QH301-705.5 Marc Rabionet Emma Polonio-Alcalá Joana Relat Marc Yeste Jennifer Sims-Mourtada April M. Kloxin Marta Planas Lidia Feliu Joaquim Ciurana Teresa Puig Fatty acid synthase as a feasible biomarker for triple negative breast cancer stem cell subpopulation cultured on electrospun scaffolds
description	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.
format	article
author	Marc Rabionet Emma Polonio-Alcalá Joana Relat Marc Yeste Jennifer Sims-Mourtada April M. Kloxin Marta Planas Lidia Feliu Joaquim Ciurana Teresa Puig
author_facet	Marc Rabionet Emma Polonio-Alcalá Joana Relat Marc Yeste Jennifer Sims-Mourtada April M. Kloxin Marta Planas Lidia Feliu Joaquim Ciurana Teresa Puig
author_sort	Marc Rabionet
title	Fatty acid synthase as a feasible biomarker for triple negative breast cancer stem cell subpopulation cultured on electrospun scaffolds
title_short	Fatty acid synthase as a feasible biomarker for triple negative breast cancer stem cell subpopulation cultured on electrospun scaffolds
title_full	Fatty acid synthase as a feasible biomarker for triple negative breast cancer stem cell subpopulation cultured on electrospun scaffolds
title_fullStr	Fatty acid synthase as a feasible biomarker for triple negative breast cancer stem cell subpopulation cultured on electrospun scaffolds
title_full_unstemmed	Fatty acid synthase as a feasible biomarker for triple negative breast cancer stem cell subpopulation cultured on electrospun scaffolds
title_sort	fatty acid synthase as a feasible biomarker for triple negative breast cancer stem cell subpopulation cultured on electrospun scaffolds
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/802999fcfc304b2a82c214d992ee0995
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Fatty acid synthase as a feasible biomarker for triple negative breast cancer stem cell subpopulation cultured on electrospun scaffolds

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