An antagonist of dishevelled protein-protein interaction suppresses β-catenin-dependent tumor cell growth

Naoaki Fujii, Liang You, Zhidong Xu, Kazutsugu Uematsu, Jufang Shan, Biao He, Iwao Mikami, Lillian R. Edmondson, Geoffrey Neale, Jie Zheng, R. Kiplin Guy, David M. Jablons

Research output: Contribution to journalArticlepeer-review

198 Scopus citations

Abstract

Recent progress in the development of inhibitors of protein-protein interactions has opened the door for developing drugs that act by novel and selective mechanisms. Building on that work, we designed a small-molecule inhibitor of the Wnt signaling pathway, which is aberrantly activated across a wide range of human tumors. The compound, named FJ9, disrupts the interaction between the Frizzed-7 Wnt receptor and the PDZ domain of Dishevelled, down-regulating canonical Wnt signaling and suppressing tumor cell growth. The antitumorigenic effects of FJ9 were pronounced, including induction of apoptosis in human cancer cell lines and tumor growth inhibition in a mouse xenograft model. FJ9 is thus among the first non-peptide inhibitors to show therapeutic efficacy through disruption of PDZ protein-protein interactions.

Original languageEnglish
Pages (from-to)573-579
Number of pages7
JournalCancer Research
Volume67
Issue number2
DOIs
StatePublished - Jan 15 2007

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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