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

被引：4

作者：

Lim, Wanyoung ^{[1
]}

Hwang, Inwoo ^{[2
]}

Zhang, Jiande ^{[3
]}

Chen, Zhenzhong ^{[3
]}

Han, Jeonghun ^{[3
]}

Jeon, Jaehyung ^{[3
]}

Koo, Bon-Kyoung ^{[4
]}

Kim, Sangmin ^{[5
]}

Lee, Jeong Eon ^{[6
]}

Kim, Youngkwan ^{[2
]}

Pienta, Kenneth J. ^{[7
]}

Amend, Sarah R. ^{[7
]}

Austin, Robert H. ^{[8
]}

Ahn, Jee-Yin ^{[2
,9
,10
]}

Park, Sungsu ^{[1
,3
,11
]}

机构：

[1] Sungkyunkwan Univ, Dept Biomed Engn, Suwon, South Korea

[2] Sungkyunkwan Univ, Sch Med, Dept Mol Cell Biol, Suwon, South Korea

[3] Sungkyunkwan Univ, Sch Mech Engn, Suwon, South Korea

[4] Vienna Bioctr VBC, Inst Mol Biotechnol, Austrian Acad Sci IMBA, Vienna, Austria

[5] Sungkyunkwan Univ, Dept Breast Canc Ctr, Samsung Med Ctr, Sch Med, Seoul, South Korea

[6] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Div Breast Surg,Dept Surg, Seoul, South Korea

[7] Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Canc Ecol Ctr, Baltimore, MD USA

[8] Princeton Univ, Dept Phys, Princeton, NJ USA

[9] Sungkyunkwan Univ, Sch Med, Single Cell Network Res Ctr, Suwon, South Korea

[10] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Samsung Biomed Res Inst, Seoul, South Korea

[11] Sungkyunkwan Univ, Inst Quantum Biophys IQB, Suwon, South Korea

来源：

ELIFE | 2024年 / 12卷

关键词：

microfluidic chip; triple negative breast cancer; polyaneuploid cancer cells; resistance; nuclear protein 1; histone deacetylase 11; Human; HISTONE DEACETYLASE 11; HDAC INHIBITORS; CHEMOTHERAPY; CARCINOMA; NUPR1; DOXORUBICIN; EXPRESSION; PREDICTOR; EMERGENCE; SURVIVAL;

D O I：

10.7554/eLife.88830

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：18

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