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

Yangzhi Liu; Kairan Yu; Keren Zhang; Mingshan Niu; Qiushi Chen; Yajie Liu; Lingyan Wang; Nana Zhang; Wenli Li; Xiaomin Zhong; Guohui Li; Sijin Wu; Jianing Zhang; Yubo Liu

doi:10.15252/embr.202256458

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

Yangzhi Liu, Kairan Yu, Keren Zhang, Mingshan Niu, Qiushi Chen, Yajie Liu, Lingyan Wang, Nana Zhang, Wenli Li, Xiaomin Zhong, Guohui Li, Sijin Wu^*, Jianing Zhang^*, Yubo Liu^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

7 Citations (Scopus)

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.

Original language	English
Article number	e56458
Journal	EMBO Reports
Volume	24
Issue number	7
DOIs	https://doi.org/10.15252/embr.202256458
Publication status	Published - 5 Jul 2023
Externally published	Yes

Keywords

O-GlcNAcylation
TOP2A
catalytic activity
chemotherapy resistance

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.15252/embr.202256458

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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",

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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

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

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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 -

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

Abstract

Keywords

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