Exploration of drug resistance mechanisms in triple negative breast cancer cells using a microfluidic device and patient tissues.
Elife
; 122024 Mar 27.
Article
em En
| MEDLINE
| ID: mdl-38536720
ABSTRACT
Chemoresistance is a major cause of treatment failure in many cancers. However, the life cycle of cancer cells as they respond to and survive environmental and therapeutic stress is understudied. In this study, we utilized a microfluidic device to induce the development of doxorubicin-resistant (DOXR) cells from triple negative breast cancer (TNBC) cells within 11 days by generating gradients of DOX and medium. In vivo chemoresistant xenograft models, an unbiased genome-wide transcriptome analysis, and a patient data/tissue analysis all showed that chemoresistance arose from failed epigenetic control of the nuclear protein-1 (NUPR1)/histone deacetylase 11 (HDAC11) axis, and high NUPR1 expression correlated with poor clinical outcomes. These results suggest that the chip can rapidly induce resistant cells that increase tumor heterogeneity and chemoresistance, highlighting the need for further studies on the epigenetic control of the NUPR1/HDAC11 axis in TNBC.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias de Mama Triplo Negativas
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article