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Updated: Feb 5, 2026

Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
A small molecule targeting myoferlin exerts promising anti-tumor effects on breast cancer
Tao Zhang1,2, Jingjie Li1,3, Yuan He1
1East 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.
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.
Insights
Researchers identified WJ460 as a potent inhibitor of breast cancer cell invasion. This small molecule targets myoferlin (MYOF), a protein crucial for breast cancer metastasis, offering a potential new therapeutic strategy.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Breast cancer metastasis is a major cause of mortality in women.
- Identifying novel therapeutic targets for metastatic breast cancer is critical.
Purpose of the Study:
- To screen for small molecule inhibitors of breast cancer cell invasion.
- To identify the molecular target of potent anti-invasive compounds.
- To evaluate the therapeutic potential of targeting myoferlin (MYOF) in breast cancer metastasis.
Main Methods:
- Small molecule library screening for anti-invasive compounds.
- Structure-activity relationship studies to optimize lead compounds.
- Proteomic and biochemical assays to identify direct molecular targets.
- Experimental metastasis mouse model to assess in vivo efficacy.
Main Results:
- WJ460 identified as a lead compound with nanomolar anti-metastatic activity in breast cancer cells.
- Myoferlin (MYOF) identified as the direct molecular target of WJ460.
- Inhibition of MYOF, by genetic means or WJ460, reduced breast cancer lung metastasis in mice.
Conclusions:
- Myoferlin (MYOF) plays an essential role in breast cancer progression and metastasis.
- Targeting MYOF with WJ460 represents a promising therapeutic strategy for metastatic breast cancer.
- MYOF is a potential molecular target for developing novel breast cancer therapies.
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