Exploration of Mechanisms of Drug Resistance in a Microfluidic Device and Patient Tissues-Reference-Cited by-同舟云学术

Exploration of Mechanisms of Drug Resistance in a Microfluidic Device and Patient Tissues

Published:2023-10-03 Issue: Volume: Page:
ISSN:
Container-title:
language:
Short-container-title:

Author:

Lim Wanyoung¹,Hwang Inwoo²,Zhang Jiande³,Chen Zhenzhong³,Han Jeonghun³,Jeon Jaehyung³,Koo Bon-Kyoung⁴^ORCID,Kim Sangmin⁵,Lee Jeong Eon⁶^ORCID,Pienta Kenneth J.⁷^ORCID,Amend Sarah R.⁷^ORCID,Austin Robert H.⁸,Ahn Jee-Yin²⁹¹⁰^ORCID,Park Sungsu¹³¹¹^ORCID

Affiliation:

1. Department of Biomedical Engineering, Sungkyunkwan University, Suwon 16419, South Korea

2. Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, South Korea

3. School of Mechanical Engineering, Sungkyunkwan University, Suwon 16419, South Korea

4. Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC), 1030 Vienna, Austria

5. Department of Breast Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, South Korea

6. Division of Breast Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, South Korea

7. The Cancer Ecology Center at the James Buchanan Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA

8. Department of Physics, Princeton University, Princeton, NJ 08544, USA

9. Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon 16419, South Korea

10. Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, South Korea

11. Institute of Quantum Biophysics (IQB), Sungkyunkwan University, Suwon 16419, South Korea

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.

Publisher

eLife Sciences Publications, Ltd

Cited by 1 articles. 订阅此论文施引文献订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献

1. Efficient separation of large particles and giant cancer cells using an isosceles trapezoidal spiral microchannel;The Analyst;2024