American Association for Cancer Research
15357163mct200130-sup-237844_3_supp_6651166_qc8xvc.docx (1.27 MB)

Supplementary Data from Disruption of SND1–MTDH Interaction by a High Affinity Peptide Results in SND1 Degradation and Cytotoxicity to Breast Cancer Cells In Vitro and In Vivo

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journal contribution
posted on 2023-04-03, 18:24 authored by Peng Li, Yunjiao He, Teng Chen, Kit-Ying Choy, Tsun Sing Chow, Iris L.K. Wong, Xinqing Yang, Wenqin Sun, Xiaochun Su, Tak-Hang Chan, Larry M.C. Chow

Figures S1 to S3


University Research Facility in Life Sciences

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Hong Kong Polytechnic University



Staphylococcal nuclease domain-containing protein 1 (SND1) is a multifunctional oncoprotein overexpressed in breast cancer. Binding of metadherin (MTDH) to SND1 results in the stabilization of SND1 and is important in the initiation and progression of breast cancer. Disruption of such interaction is a potential therapeutic for breast cancer. SN1/2 domain of SND1 was used as bait in a phage display screening to identify a 12-amino acid peptide 4-2. The activity of peptide 4-2 was evaluated by ELISA, coimmunoprecipitation, MTS, Western blot analysis, and xenograft mouse model. Peptide 4-2 could disrupt SND1–MTDH interaction. Cell penetrating derivative of peptide 4–2 (CPP-4–2) could penetrate and kill breast cancer cells by disrupting SND1–MTDH interaction and degrading SND1. Tryptophan 10 (W10) of peptide 4-2 was essential in mediating cytotoxicity, SND1 interaction, SND1–MTDH disruption, and SND1 degradation. CPP-4-2 could inhibit the growth of breast cancer in a xenograft mouse model. The SND1-interacting peptide 4-2 could kill breast cancer cells both in vitro and in vivo by interacting with SND1, disrupting SND1–MTDH interaction, and inducing SND1 degradation. W10 was an essential amino acid in the activity of peptide 4-2.