Exploration of drug resistance mechanisms in triple negative breast cancer cells using a microfluidic device and patient tissues

Wanyoung Lim, Inwoo Hwang, Jiande Zhang, Zhenzhong Chen, Jeonghun Han, Jaehyung Jeon, Bon Kyoung Koo, Sangmin Kim, Jeong Eon Lee, Youngkwan Kim, Kenneth J. Pienta, Sarah R. Amend, Robert H. Austin, Jee Yin Ahn, Sungsu Park

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article numberRP88830
JournaleLife
Volume12
DOIs
StatePublished - Mar 2024

All Science Journal Classification (ASJC) codes

  • General Immunology and Microbiology
  • General Biochemistry, Genetics and Molecular Biology
  • General Neuroscience

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