A state-of-the-art review on LSD1 and its inhibitors in breast cancer: Molecular mechanisms and therapeutic significance

Guan-Jun Yang; Yan-Jun Liu; Li-Jian Ding; Fan Tao; Ming-Hui Zhu; Zhen-Yuan Shi; Juan-Ming Wen; Meng-Yao Niu; Xiang Li; Zhan-Song Xu; Wan-Jia Qin; Chen-Jie Fei; Jiong Chen

doi:10.3389/fphar.2022.989575

A state-of-the-art review on LSD1 and its inhibitors in breast cancer: Molecular mechanisms and therapeutic significance

Front Pharmacol. 2022 Sep 16:13:989575. doi: 10.3389/fphar.2022.989575. eCollection 2022.

Authors

Guan-Jun Yang^{1

2

3}, Yan-Jun Liu², Li-Jian Ding⁴, Fan Tao², Ming-Hui Zhu², Zhen-Yuan Shi², Juan-Ming Wen², Meng-Yao Niu², Xiang Li², Zhan-Song Xu², Wan-Jia Qin², Chen-Jie Fei^{1

2

3}, Jiong Chen^{1

2

3}

Affiliations

¹ State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Ningbo University, Ningbo, Zhejiang, China.
² Laboratory of Biochemistry and Molecular Biology, School of Marine Sciences, Ningbo University, Ningbo, China.
³ Key Laboratory of Aquacultural Biotechnology Ministry of Education, Ningbo University, Ningbo, China.
⁴ Li Dak Sum Yip Yio Chin Kenneth Li Marine Biopharmaceutical Research Center, Department of Marine Pharmacy, College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo, China.

Abstract

Breast cancer (BC) is a kind of malignant cancer in women, and it has become the most diagnosed cancer worldwide since 2020. Histone methylation is a common biological epigenetic modification mediating varieties of physiological and pathological processes. Lysine-specific demethylase 1 (LSD1), a first identified histone demethylase, mediates the removal of methyl groups from histones H3K4me1/2 and H3K9me1/2 and plays a crucial role in varieties of cancer progression. It is also specifically amplified in breast cancer and contributes to BC tumorigenesis and drug resistance via both demethylase and non-demethylase manners. This review will provide insight into the overview structure of LSD1, summarize its action mechanisms in BC, describe the therapeutic potential of LSD1 inhibitors in BC, and prospect the current opportunities and challenges of targeting LSD1 for BC therapy.

Keywords: H3K4me1/2; H3K9me1/2; LSD1; breast cancer; histone demethylase; inhibitors.

Publication types

Review