2. Academic Validation
  3. A small molecule targeting myoferlin exerts promising anti-tumor effects on breast cancer

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

  • Nat Commun. 2018 Sep 13;9(1):3726. doi: 10.1038/s41467-018-06179-0.
Tao Zhang 1 2,  Jingjie Li 1 3,  Yuan He 1,  Feifei Yang 1,  Yun Hao 1,  Wangrui Jin 1,  Jing Wu 1,  Zhenliang Sun 4,  Yunqi Li 1,  Yihua Chen 5,  Zhengfang Yi 6 7,  Mingyao Liu 8 9
Affiliations

Affiliations

  • 1 East China Normal University and Shanghai Fengxian District Central Hospital Joint Center for Translational Medicine, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 200241, Shanghai, China.
  • 2 Department of Orthopaedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 200080, Shanghai, China.
  • 3 The Institute of Cell Metabolism and Disease, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 200080, Shanghai, China.
  • 4 Shanghai University of Medicine & Health Sciences Affiliated Sixth People's Hospital South Campus, Shanghai, 201499, China.
  • 5 East China Normal University and Shanghai Fengxian District Central Hospital Joint Center for Translational Medicine, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 200241, Shanghai, China. yhchen@bio.ecnu.edu.cn.
  • 6 East China Normal University and Shanghai Fengxian District Central Hospital Joint Center for Translational Medicine, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 200241, Shanghai, China. zfyi@bio.ecnu.edu.cn.
  • 7 Shanghai University of Medicine & Health Sciences Affiliated Sixth People's Hospital South Campus, Shanghai, 201499, China. zfyi@bio.ecnu.edu.cn.
  • 8 East China Normal University and Shanghai Fengxian District Central Hospital Joint Center for Translational Medicine, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 200241, Shanghai, China. myliu@bio.ecnu.edu.cn.
  • 9 Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M University Health Science Center, 77030, Houston, USA. myliu@bio.ecnu.edu.cn.
PMID: 30213946 DOI: 10.1038/s41467-018-06179-0
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.

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