MYSM1 induces apoptosis and sensitizes TNBC cells to cisplatin via RSK3-phospho-BAD pathway

Xiaolin Guan; Xin Meng; Keyu Zhu; Jinyan Kai; Yixuan Liu; Qian Ma; Ying Tong; Hui Zheng; Suhong Xie; Xiaolu Ma; Yanchun Wang; Renquan Lu; Lin Guo

doi:10.1038/s41420-022-00881-1

MYSM1 induces apoptosis and sensitizes TNBC cells to cisplatin via RSK3-phospho-BAD pathway

Cell Death Discov. 2022 Feb 26;8(1):84. doi: 10.1038/s41420-022-00881-1.

Authors

Xiaolin Guan^#^{1

2}, Xin Meng^#^{1

2}, Keyu Zhu^{1

2}, Jinyan Kai^{1

2}, Yixuan Liu^{1

2}, Qian Ma^{1

2}, Ying Tong¹, Hui Zheng^{1

2}, Suhong Xie¹, Xiaolu Ma¹, Yanchun Wang³, Renquan Lu^{4

5}, Lin Guo^{6

7}

Affiliations

¹ Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China.
² Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
³ Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China. springor1988@alumni.sjtu.edu.cn.
⁴ Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China. renquanlu@fudan.edu.cn.
⁵ Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. renquanlu@fudan.edu.cn.
⁶ Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China. guolin500@hotmail.com.
⁷ Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. guolin500@hotmail.com.

^# Contributed equally.

Abstract

Breast cancer is one of the leading causes of mortality among women. Triple-negative breast cancer (TNBC) is responsible for a large percentage of all breast cancer deaths in women. This study demonstrated the function of Myb-like, SWIRM, and MPN domains 1 (MYSM1), an H2A deubiquitinase (DUB), in TNBC. MYSM1 expression was drastically decreased in breast cancer, especially in TNBC, suggesting a potential anticancer effect. Overexpressing and suppressing MYSM1 expression in TNBC cell lines led to significant biological changes in cell proliferation. Furthermore, MYSM1 overexpression increased cisplatin-induced apoptosis, which might be attributed to RSK3 inactivation and the subsequently decreased phosphorylation of Bcl-2 antagonist of cell death (BAD) (Ser 112). The findings suggest that MYSM1 is a potential target for regulating cell apoptosis and suppressing resistance to cisplatin in TNBC.

Publication types

Editorial

Abstract

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