Overexpression of PBK/TOPK relates to tumour malignant potential and poor outcome of gastric carcinoma
Menée sur 5 lignées cellulaires de cancer gastrique et à l'aide de 144 pièces de résection prélevées sur des patients atteints d'une tumeur primitive de l'estomac, cette étude met en évidence une relation entre la surexpression de la sérine-thréonine kinase PBK/TOPK et l'agressivité de la tumeur ou la survie des patients
Background : PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK) is a serine–threonine kinase and overexpressed in various types of cancer by inhibiting the transactivation activities of p53 and PTEN. We tested whether PBK/TOPK acts as a cancer-promoting gene through its activation/overexpression in gastric cancer (GC).
Methods : We analysed five GC cell lines and 144 primary tumours, which were curatively resected in our hospital between 2001 and 2003.
Results : Overexpression of the PBK/TOPK protein was frequently detected in GC cell lines (4 out of 5 lines, 80.0%) was detected in primary tumour samples of GC (24 out of 144 cases, 16.6%) and was significantly correlated with venous invasion, tumour depth and recurrence rate. PDZ-binding kinase/T-LAK cell-originated protein kinase-overexpressing tumours had a worse survival rate than those with non-expressing tumours (P=0.0009, log-rank test). PDZ-binding kinase/T-LAK cell-originated protein kinase positivity was independently associated with a worse outcome in multivariate analysis (P<0.0001, hazard ratio 6.40 (2.71–14.49)). In PBK/TOPK-overexpressing GC cells, knockdown of PBK/TOPK inhibited the cell proliferation through the p53 activation in a TP53 mutation-dependent manner and inhibited the migration/invasion through the PTEN upregulation in a TP53 mutation-independent manner.
Conclusions : These findings suggest PBK/TOPK plays a crucial role in tumour malignant potential through its overexpression and highlight its usefulness as a prognostic factor and potential therapeutic target in GC.
British Journal of Cancer , résumé, 2015