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  • Exploration of drug resistance mechanisms in triple negative breast cancer cells using a microfluidic device and patient tissues
Title: Exploration of drug resistance mechanisms in triple negative breast cancer cells using a microfluidic device and patient tissues
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 highNUPR1expression 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.  more » « less
Award ID(s):
1734030
PAR ID:
10572791
Author(s) / Creator(s):
; ; ; ; ; ; ; ; ; ; ; ; ; ;
Publisher / Repository:
eLife
Date Published:
Journal Name:
eLife
Volume:
12
ISSN:
2050-084X
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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