4.8 Article

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

Journal

MATERIALS TODAY BIO
Volume 12, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.mtbio.2021.100155

Keywords

Triple negative breast cancer; Three-dimensional cell culture; Polycaprolactone; Electrospun scaffolds; Breast cancer stem cells; Fatty acid synthase

Funding

  1. Ministerio de Economia y Competitividad [DPI2016-77156R]
  2. Catalan Government [2017SGR00385]
  3. Oncolliga Foundation
  4. Delaware INBRE program
  5. National Institute of General Medical Sciences -NIGMS from the National Institutes of Health [P20 GM103446]
  6. State of Delaware
  7. Marc Rabionet pre-doctoral grant [IFUdG2017/62]
  8. Emma Polonio-Alcala pre-doctoral grant [2019FI_B01011]
  9. Fundacion Ramon Areces
  10. Instituto de Salud Carlos III
  11. European Union (ERDF/ESF, A way to make Europe/Investing in your future) [PI19/00372]

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Research has found a potential novel target for TNBC treatment by focusing on breast cancer stem cells, using three-dimensional scaffolds to maintain stemness and alter cell signaling pathways. Additionally, inhibition of fatty acid synthase was shown to reduce stem cell population, overcoming the expansion seen in 3D culture.
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 stemnessenriched 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.

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