A small molecule targeting myoferlin exerts promising anti-tumor effects on breast cancer

Tao Zhang, Jingjie Li, Yuan He, Feifei Yang, Yun Hao, Wangrui Jin, Jing Wu, Zhenliang Sun, Yunqi Li, Yihua Chen (), Zhengfang Yi () and Mingyao Liu ()
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Tao Zhang: East China Normal University
Jingjie Li: East China Normal University
Yuan He: East China Normal University
Feifei Yang: East China Normal University
Yun Hao: East China Normal University
Wangrui Jin: East China Normal University
Jing Wu: East China Normal University
Zhenliang Sun: Shanghai University of Medicine & Health Sciences Affiliated Sixth Peopleʼs Hospital South Campus
Yunqi Li: East China Normal University
Yihua Chen: East China Normal University
Zhengfang Yi: East China Normal University
Mingyao Liu: East China Normal University

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: Abstract Breast cancer is one of the most lethal cancers in women when it reaches the metastatic stage. Here, we screen a library of small molecules for inhibitors of breast cancer cell invasion, and use structure/activity relationship studies to develop a series of small molecules with improved activity. We find WJ460 as one of the lead compounds exerting anti-metastatic activity in the nanomolar range in breast cancer cells. Proteomic and biochemical studies identify myoferlin (MYOF) as the direct target of WJ460. In parallel, loss of MYOF or pharmacological inhibition of MYOF by WJ460 reduces breast cancer extravasation into the lung parenchyma in an experimental metastasis mouse model, which reveals an essential role of MYOF in breast cancer progression. Our findings suggest that MYOF can be explored as a molecular target in breast cancer metastasis and that targeting MYOF by WJ460 may be a promising therapeutic strategy in MYOF-driven cancers.

Date: 2018
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DOI: 10.1038/s41467-018-06179-0

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