Oncotarget

Research Papers:

NDRG2 promotes adriamycin sensitivity through a Bad/p53 complex at the mitochondria in breast cancer

Yifang Wei, Shentong Yu, Yongping Zhang, Yuan Zhang, Huadong Zhao, Zhixiong Xiao, Libo Yao, Suning Chen and Jian Zhang _

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Oncotarget. 2017; 8:29038-29047. https://doi.org/10.18632/oncotarget.16035

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Abstract

Yifang Wei1,*, Shentong Yu1,2,*, Yongping Zhang3,*, Yuan Zhang4, Huadong Zhao5, Zhixiong Xiao6, Libo Yao1, Suning Chen1,7, Jian Zhang1

1State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi’an, 710032, Shaanxi, China

2Department of Pathology, The Fourth Military Medical University, Xi’an, 710032, Shaanxi, China

3Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, 310058, Hangzhou, China

4Department of Oncology, The State Key Discipline of Cell Biology, Xijing Hospital, The Fourth Military Medical University, Xi’an, 710032, Shaanxi, China

5Department of General Surgery, Tangdu Hospital, The Fourth Military Medical University, 710038, Xi’an, China

6College of Life Science, Sichuan University, Chendu, 610065, Sichuan, China

7Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Xi’an, 710032, Shaanxi, China

*These authors have contributed equally to this work

Correspondence to:

Jian Zhang, email: biozhangj@fmmu.edu.cn

Suning Chen, email: chensning78@163.com

Libo Yao, email: bioyao@fmmu.edu.cn

Keywords: NDRG2, P53, Bad, chemotherapy resistance, breast cancer

Abbreviations: NDRG2, N-Myc downstream regulated gene 2; ADR, Adriamycin; ABC, ATP-Binding Cassette

Received: December 05, 2016    Accepted: February 20, 2017    Published: March 09, 2017

ABSTRACT

Chemo-resistance presents a difficult challenge for the treatment of breast cancer. Our previous study showed that N-Myc downstream-regulated gene 2 (NDRG2) is involved in p53-mediated apoptosis induced by chemotherapy, through a mechanism that has so far remained obscure. Here, we explored the role of NDRG2 in chemo-resistance with a focus on Adriamycin (ADR) and found that NDRG2 expression decreased in ADR resistance breast cancer cells. Interestingly, NDRG2 can promote ADR sensitivity by inhibiting proliferation, enhancing cellular damage responses, and promoting apoptosis in a p53-dependent manner. We also found that NDRG2 could upregulate Bad expression by increasing its half-life, which is associated with p53 to mitochondria. Hence, our collective data provided the first evidence that NDRG2 promoting sensitivity of breast cancer is dependent on p53 by preventing p53 from entering the nucleus rather than changing its expression.


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