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

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.

SUBMITTER: Zhang T

PROVIDER: S-EPMC6137146 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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

Zhang Tao T Li Jingjie J He Yuan Y Yang Feifei F Hao Yun Y Jin Wangrui W Wu Jing J Sun Zhenliang Z Li Yunqi Y Chen Yihua Y Chen Yihua Y Yi Zhengfang Z Liu Mingyao M

Nature communications 20180913 1

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 targ ...[more]

PMID: 30213946

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

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

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