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Overexpression of PBK/TOPK relates to tumour malignant potential and poor outcome of gastric carcinoma.

ABSTRACT:

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.

SUBMITTER: Ohashi T

PROVIDER: S-EPMC5243986 | biostudies-literature |

REPOSITORIES: biostudies-literature

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