Liu, Y., Yu, K., Zhang, K., Niu, M., Chen, Q., Liu, Y., Wang, L., Zhang, N., Li, W., Zhong, X., Li, G., Wu, S., Zhang, J., & Liu, Y. (2023). O-GlcNAcylation promotes topoisomerase IIα catalytic activity in breast cancer chemoresistance. EMBO Reports, 24(7), Article e56458. https://doi.org/10.15252/embr.202256458
Liu, Yangzhi ; Yu, Kairan ; Zhang, Keren et al. / O-GlcNAcylation promotes topoisomerase IIα catalytic activity in breast cancer chemoresistance. In: EMBO Reports. 2023 ; Vol. 24, No. 7.
@article{f39571e080ee48b9a9a74590811e725f,
title = "O-GlcNAcylation promotes topoisomerase IIα catalytic activity in breast cancer chemoresistance",
abstract = "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.",
keywords = "O-GlcNAcylation, TOP2A, catalytic activity, chemotherapy resistance",
author = "Yangzhi Liu and Kairan Yu and Keren Zhang and Mingshan Niu and Qiushi Chen and Yajie Liu and Lingyan Wang and Nana Zhang and Wenli Li and Xiaomin Zhong and Guohui Li and Sijin Wu and Jianing Zhang and Yubo Liu",
note = "Publisher Copyright: {\textcopyright} 2023 The Authors.",
year = "2023",
month = jul,
day = "5",
doi = "10.15252/embr.202256458",
language = "English",
volume = "24",
journal = "EMBO Reports",
issn = "1469-221X",
number = "7",
}
Liu, Y, Yu, K, Zhang, K, Niu, M, Chen, Q, Liu, Y, Wang, L, Zhang, N, Li, W, Zhong, X, Li, G, Wu, S, Zhang, J & Liu, Y 2023, 'O-GlcNAcylation promotes topoisomerase IIα catalytic activity in breast cancer chemoresistance', EMBO Reports, vol. 24, no. 7, e56458. https://doi.org/10.15252/embr.202256458
O-GlcNAcylation promotes topoisomerase IIα catalytic activity in breast cancer chemoresistance. / Liu, Yangzhi; Yu, Kairan; Zhang, Keren et al.
In:
EMBO Reports, Vol. 24, No. 7, e56458, 05.07.2023.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - O-GlcNAcylation promotes topoisomerase IIα catalytic activity in breast cancer chemoresistance
AU - Liu, Yangzhi
AU - Yu, Kairan
AU - Zhang, Keren
AU - Niu, Mingshan
AU - Chen, Qiushi
AU - Liu, Yajie
AU - Wang, Lingyan
AU - Zhang, Nana
AU - Li, Wenli
AU - Zhong, Xiaomin
AU - Li, Guohui
AU - Wu, Sijin
AU - Zhang, Jianing
AU - Liu, Yubo
N1 - Publisher Copyright:
© 2023 The Authors.
PY - 2023/7/5
Y1 - 2023/7/5
N2 - 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.
AB - 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.
KW - O-GlcNAcylation
KW - TOP2A
KW - catalytic activity
KW - chemotherapy resistance
UR - http://www.scopus.com/inward/record.url?scp=85161590322&partnerID=8YFLogxK
U2 - 10.15252/embr.202256458
DO - 10.15252/embr.202256458
M3 - Article
C2 - 37249035
AN - SCOPUS:85161590322
SN - 1469-221X
VL - 24
JO - EMBO Reports
JF - EMBO Reports
IS - 7
M1 - e56458
ER -
Liu Y, Yu K, Zhang K, Niu M, Chen Q, Liu Y et al. O-GlcNAcylation promotes topoisomerase IIα catalytic activity in breast cancer chemoresistance. EMBO Reports. 2023 Jul 5;24(7):e56458. doi: 10.15252/embr.202256458
