| Literature DB >> 28759015 |
Haiming Jiang1, Rong Deng1,2, Xiuyan Yang1, Jialin Shang1, Shaoyong Lu1, Yanlong Zhao1, Kun Song1, Xinyi Liu1,3, Qiufen Zhang1,3, Yu Chen4, Y Eugene Chinn5, Geng Wu6, Jian Li7, Guoqiang Chen1,5, Jianxiu Yu1,2, Jian Zhang1,3.
Abstract
The 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.Entities:
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Year: 2017 PMID： 28759015 DOI： 10.1038/nchembio.2442
Source DB: PubMed Journal: Nat Chem Biol ISSN： 1552-4450 Impact factor: 15.040