In:
Cancer Science, Wiley, Vol. 108, No. 5 ( 2017-05), p. 1049-1057
Abstract:
CUB domain‐containing protein‐1 ( CDCP 1) is a trans‐membrane protein predominantly expressed in various cancer cells and involved in tumor progression. CDCP 1 is phosphorylated at tyrosine residues in the intracellular domain by Src family kinases and recruits PKC δ to the plasma membrane through tyrosine phosphorylation‐dependent association with the C2 domain of PKC δ, which in turn induces a survival signal in an anchorage‐independent condition. In this study, we used our cell‐free screening system to identify a small compound, glycoconjugated palladium complex (Pd‐Oqn), which significantly inhibited the interaction between the C2 domain of PKC δ and phosphorylated CDCP 1. Immunoprecipitation assays demonstrated that Pd‐Oqn hindered the intercellular interaction of phosphorylated CDCP 1 with PKC δ and also suppressed the phosphorylation of PKC δ but not that of ERK or AKT . In addition, Pd‐Oqn inhibited the colony formation of gastric adenocarcinoma 44As3 cells in soft agar as well as their invasion. In mouse models, Pd‐Oqn markedly reduced the peritoneal dissemination of gastric adenocarcinoma cells and the tumor growth of pancreatic cancer orthotopic xenografts. These results suggest that the novel compound Pd‐Oqn reduces tumor metastasis and growth by inhibiting the association between CDCP 1 and PKC δ, thus potentially representing a promising candidate among therapeutic reagents targeting protein–protein interaction.
Type of Medium:
Online Resource
ISSN:
1347-9032
,
1349-7006
DOI:
10.1111/cas.2017.108.issue-5
Language:
English
Publisher:
Wiley
Publication Date:
2017
detail.hit.zdb_id:
2115647-5
detail.hit.zdb_id:
2111204-6
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