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Exploration of Mechanisms of DrugResistance in a Microfluidic Device andPatient Tissues

ABSTRACT: Chemoresistance is a major cause of treatment failure in many cancers. However, the lifecycle of cancer cells as they respond to and survive environmental and therapeutic stress isunderstudied. In this study, we utilized a microfluidic device to induce the development ofdoxorubicin-resistant (DOXR) cells from triple negative breast cancer (TNBC) cells within 11days by generating gradients of DOX and medium. In vivo chemoresistant xenograft models,an unbiased genome-wide transcriptome analysis, and a patient data/tissue analysis allshowed that chemoresistance arose from failed epigenetic control of the nuclear protein-1(NUPR1)/histone deacetylase 11 (HDAC11) axis, and high Nupr1 expression correlated withpoor clinical outcomes. These results suggest that the chip can rapidly induce resistant cellsthat increase tumor heterogeneity and chemoresistance, highlighting the need for furtherstudies on the epigenetic control of the NUPR1/HDAC11 axis in TNBC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE256086 | GEO | 2024/02/24

REPOSITORIES: GEO

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