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
| Autor: | Teng Chen, Xiaochun Su, Tak Hang Chan, Wenqin Sun, Peng Li, Tsun Sing Chow, Larry M.C. Chow, Iris L. K. Wong, Kit Ying Choy, Xinqing Yang, Yunjiao He |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
chemistry.chemical_classification Cancer Research Phage display Chemistry Cell MTDH Peptide medicine.disease In vitro 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Breast cancer Oncology In vivo 030220 oncology & carcinogenesis Cancer research medicine Cytotoxicity |
| Zdroj: | Molecular Cancer Therapeutics. 20:76-84 |
| ISSN: | 1538-8514 1535-7163 |
| DOI: | 10.1158/1535-7163.mct-20-0130 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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