Peptidomimetic inhibitors of APC-Asef interaction block colorectal cancer migration
Jiang, Haiming; Deng, Rong1; Yang, Xiuyan; Shang, Jialin; Lu, Shaoyong; Zhao, Yanlong; Song, Kun; Liu, Xinyi2; Zhang, Qiufen2; Chen, Yu3; Chinn, Y. Eugene; Wu, Geng6; Li, Jian7; Chen, Guoqiang4,5; Yu, Jianxiu1; Zhang, Jian2
AbstractThe binding of adenomatous polyposis coli (APC) to its receptor Asef relieves the negative intramolecular regulation of Asef and leads to aberrant cell migration in human colorectal cancer. Because of its crucial role in metastatic dissemination, the interaction between APC and Asef is an attractive target for anti-colorectal-cancer therapy. We rationally designed a series of peptidomimetics that act as potent inhibitors of the APC interface. Crystal structures and biochemical and cellular assays showed that the peptidomimetics in the APC pocket inhibited the migration of colorectal cells by disrupting APC-Asef interaction. By using the peptidomimetic inhibitor as a chemical probe, we found that CDC42 was the downstream GTPase involved in APC-stimulated Asef activation in colorectal cancer cells. Our work demonstrates the feasibility of exploiting APC-Asef interaction to regulate the migration of colorectal cancer cells, and provides what to our knowledge is the first class of protein-protein interaction inhibitors available for the development of cancer therapeutics targeting APC-Asef signaling.
WOS IDWOS:000407929800017
EI Accession Number1552-4469
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Cited Times:28[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Affiliation1.Shanghai Jiao Tong Univ, Sch Med, Minist Educ, Dept Pathophysiol,Key Lab Cell Differentiat & Apo, Shanghai, Peoples R China
2.Shanghai Jiao Tong Univ, Sch Med, Shanghai Key Lab Tumor Microenvironm & Inflammat, Dept Biochem & Mol Cell Biol,State Key Lab Oncoge, Shanghai, Peoples R China
3.Shanghai Jiao Tong Univ, Sch Med, Med Bioinformat Ctr, Shanghai, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Ceram, State Key Lab High Performance Ceram & Superfine, Shanghai, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Shanghai, Peoples R China
6.Shanghai Jiao Tong Univ, Sch Med, Shanghai, Peoples R China
7.Shanghai Jiao Tong Univ, State Key Lab Microbial Metab, Shanghai, Peoples R China
8.East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai, Peoples R China
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GB/T 7714
Jiang, Haiming,Deng, Rong,Yang, Xiuyan,et al. Peptidomimetic inhibitors of APC-Asef interaction block colorectal cancer migration[J]. NATURE CHEMICAL BIOLOGY,2017,13(9):994.
APA Jiang, Haiming.,Deng, Rong.,Yang, Xiuyan.,Shang, Jialin.,Lu, Shaoyong.,...&Zhang, Jian.(2017).Peptidomimetic inhibitors of APC-Asef interaction block colorectal cancer migration.NATURE CHEMICAL BIOLOGY,13(9),994.
MLA Jiang, Haiming,et al."Peptidomimetic inhibitors of APC-Asef interaction block colorectal cancer migration".NATURE CHEMICAL BIOLOGY 13.9(2017):994.
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