O-GlcNAcylation promotes topoisomerase IIα catalytic activity in breast cancer chemoresistance

Liu，Yangzhi1; Yu，Kairan1; Zhang，Keren2; Niu，Mingshan3; Chen，Qiushi4,5; Liu，Yajie1; Wang，Lingyan1; Zhang，Nana1; Li，Wenli1; Zhong，Xiaomin6; Li，Guohui7; Wu，Sijin7; Zhang，Jianing1; Liu，Yubo1

2023-07-05

10.15252/embr.202256458

EMBO Reports   影响因子和分区

1469-221X

1469-3178

DNA topoisomerase IIα (TOP2A) plays a vital role in replication and cell division by catalytically altering DNA topology. It is a prominent target for anticancer drugs, but clinical efficacy is often compromised due to chemoresistance. In this study, we investigate the role of TOP2A O-GlcNAcylation in breast cancer cells and patient tumor tissues. Our results demonstrate that elevated TOP2A, especially its O-GlcNAcylation, promotes breast cancer malignant progression and resistance to adriamycin (Adm). O-GlcNAcylation at Ser1469 enhances TOP2A chromatin DNA binding and catalytic activity, leading to resistance to Adm in breast cancer cells and xenograft models. Mechanistically, O-GlcNAcylation-modulated interactions between TOP2A and cell cycle regulators influence downstream gene expression and contribute to breast cancer drug resistance. These results reveal a previously unrecognized mechanistic role for TOP2A O-GlcNAcylation in breast cancer chemotherapy resistance and provide support for targeting TOP2A O-GlcNAcylation in cancer therapy.

catalytic activity chemotherapy resistance O-GlcNAcylation TOP2A

SCI

英语

其他

National Natural Science Foundation of China[32171282];Fundamental Research Funds for the Central Universities[DUT22YG131];

Biochemistry & Molecular Biology ; Cell Biology

Biochemistry & Molecular Biology ; Cell Biology

WOS:000997031600001

WILEY

MOLECULAR BIOLOGY & GENETICS

2-s2.0-85161590322

Scopus

1.School of Life and Pharmaceutical Sciences,Dalian University of Technology,Panjin,China
2.Department of Chemistry,College of Science,Southern University of Science and Technology,Shenzhen,China
3.Blood Diseases Institute,Xuzhou Medical University,Xuzhou,Jiangsu,China
4.Department of Chemistry,The University of Hong Kong,Hong Kong
5.Laboratory for Synthetic Chemistry and Chemical Biology Limited,Hong Kong Science Park,Hong Kong
6.Department of Oncology,The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University,Huai'an,China
7.Laboratory of Molecular Modeling and Design,State Key Laboratory of Molecular Reaction Dynamics,Dalian Institute of Chemical Physics,Chinese Academy of Sciences,Dalian,China

Liu，Yangzhi,Yu，Kairan,Zhang，Keren,et al. O-GlcNAcylation promotes topoisomerase IIα catalytic activity in breast cancer chemoresistance[J]. EMBO Reports,2023,24(7).

Liu，Yangzhi.,Yu，Kairan.,Zhang，Keren.,Niu，Mingshan.,Chen，Qiushi.,...&Liu，Yubo.(2023).O-GlcNAcylation promotes topoisomerase IIα catalytic activity in breast cancer chemoresistance.EMBO Reports,24(7).

Liu，Yangzhi,et al."O-GlcNAcylation promotes topoisomerase IIα catalytic activity in breast cancer chemoresistance".EMBO Reports 24.7(2023).