@article{204201,
  keywords = {Animals, Humans, Transcription Factors, Membrane Proteins, Mice, Cell Adhesion Molecules, RNA-Binding Proteins, Endonucleases, Triple Negative Breast Neoplasms, Micrococcal Nuclease},
  author = {Minhong Shen and Yong Wei and Hahn Kim and Liling Wan and Yi-Zhou Jiang and Xiang Hang and Michael Raba and Stacy Remiszewski and Michelle Rowicki and Cheng-Guo Wu and Songyang Wu and Lanjing Zhang and Xin Lu and Min Yuan and Heath Smith and Aiping Zheng and Joseph Bertino and John Jin and Yongna Xing and Zhi-Ming Shao and Yibin Kang},
  title = {Small-molecule inhibitors that disrupt the MTDH-SND1 complex suppress breast cancer progression and metastasis},
  abstract = {<p>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.</p>
},
  year = {2022},
  journal = {Nat Cancer},
  volume = {3},
  pages = {43-59},
  month = {01/2022},
  issn = {2662-1347},
  doi = {10.1038/s43018-021-00279-5},
  language = {eng},
}