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- W3216702981 abstract "Metastatic breast cancer is a leading health burden worldwide. Previous studies have shown that metadherin (MTDH) promotes breast cancer initiation, metastasis and therapy resistance; however, the therapeutic potential of targeting MTDH remains largely unexplored. Here, we used genetically modified mice and demonstrate that genetic ablation of Mtdh inhibits breast cancer development through disrupting the interaction with staphylococcal nuclease domain-containing 1 (SND1), which is required to sustain breast cancer progression in established tumors. We performed a small-molecule compound screening to identify a class of specific inhibitors that disrupts the protein–protein interaction (PPI) between MTDH and SND1 and show that our lead candidate compounds C26-A2 and C26-A6 suppressed tumor growth and metastasis and enhanced chemotherapy sensitivity in preclinical models of triple-negative breast cancer (TNBC). Our results demonstrate a significant therapeutic potential in targeting the MTDH–SND1 complex and identify a new class of therapeutic agents for metastatic breast cancer. Kang and colleagues identify a specific compound blocking MTDH1–SND1 interaction, which prevents metastatic breast cancer progression, induces regression of established metastasis in preclinical models and restores chemosensitivity." @default.
- W3216702981 created "2021-12-06" @default.
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- W3216702981 date "2021-11-29" @default.
- W3216702981 modified "2023-10-14" @default.
- W3216702981 title "Small-molecule inhibitors that disrupt the MTDH–SND1 complex suppress breast cancer progression and metastasis" @default.
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- W3216702981 doi "https://doi.org/10.1038/s43018-021-00279-5" @default.
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