Open AccessExpression of aurora kinase A correlates with the Wnt‐modulator RACGAP 1 in gastric cancer
Author(s) -
Bornschein Jan,
Nielitz Jessica,
Drozdov Ignat,
Selgrad Michael,
Wex Thomas,
Jechorek Doerthe,
Link Alexander,
Vieth Michael,
Malfertheiner Peter
Publication year - 2016
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.610
Subject(s) - wnt signaling pathway , cancer research , cancer , carcinogenesis , biology , immunohistochemistry , colorectal cancer , gene , immunology , genetics
Canonical Wnt signaling is involved in gastric carcinogenesis. The aim of this study was to identify the link between Wnt signaling and aurora kinase A ( AURKA ), a target for the treatment of gastrointestinal cancers. Publicly available microarray data were used to identify phenotype‐specific protein–protein interaction ( PPI ) subnetworks. The in silico analysis revealed a gastric cancer‐specific PPI subnetwork consisting of 2745 proteins and 50,935 interactions. We focused on the link of AURKA to a Wnt‐specific interaction module consisting of 92 proteins. There was a direct association of AURKA with Rac GTPase‐activating protein 1 ( RACGAP 1), as well as with CTNBB 1 ( β ‐catenin) and CDKN 1A as second‐order interactors. Differential expression analysis revealed a significant downregulation of both AURKA and RACGAP 1 in gastric cancer compared to noncancer controls. Biopsies from a prospective cohort of 56 patients with gastric cancer (32 intestinal type, 24 diffuse type) and 20 noncancer controls were used for validation of the identified targets. The RT ‐ PCR data confirmed a strong correlation of AURKA and RACGAP 1 gene expression both in the tumor, the tumor‐adjacent and the tumor‐distant mucosa. RACGAP 1 in the tumor was also associated with CTNBB 1 expression, and inversely associated with CDKN 1A gene expression. Immunohistochemistry confirmed expression of the RACGAP 1 protein in gastric cancer and the tumor‐adjacent mucosa. RACGAP 1 expression was not associated with tumor stage, grading, Lauren type, Helicobacter pylori infection, or age. In conclusion, AURKA is directly associated with the expression of RACGAP 1, a modulator of the canonical Wnt signaling pathway.