ONCOmmunity

Overexpression of PBK/TOPK Contributes to Tumor Development and Poor Outcome of Esophageal Squamous Cell Carcinoma.

By: Takuma Ohashi, Shuhei Komatsu, Daisuke Ichikawa, Mahito Miyamae, Wataru Okajima, Taisuke Imamura, Jun Kiuchi, Keiji Nishibeppu, Toshiyuki Kosuga, Hirotaka Konishi, Atsushi Shiozaki, Hitoshi Fujiwara, Kazuma Okamoto, Hitoshi Tsuda, Eigo Otsuji

Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kyoto, Japan.
2016-10-02; doi:

Abstract

Background

PDZ-binding kinase/T-cell-originated protein kinase (PBK/TOPK) is a serine-threonine kinase and overexpressed in various types of cancer. PBK/TOPK is associated with tumor cell development and progression through suppression of p53 function. In this study, we tested whether PBK acts as a cancer-promoting factor by being overexpressed in esophageal squamous cell carcinoma (ESCC).

Materials

We analyzed PBK/TOPK expression in 15 ESCC cell lines, and 54 primary ESCC tumors that were curatively resected between 1994 and 2007.

Results

Overexpression of the PBK/TOPK protein was detected in 93% (14/15) ESCC cell lines and 19% (10/54) primary ESCC tumor samples, and significantly correlated with macroscopic appearance and tumor depth. PBK/TOPK positivity was independently associated with worse outcome in multivariate analysis (p=0.0235, hazard ratio=3.58). Knockdown of PBK/TOPK using specific siRNAs inhibited the cell proliferation, invasion/migration of PBK/TOPK-overexpressing ESCC cell lines.

Conclusion

These findings suggest that PBK/TOPK plays a crucial role in tumor malignant potential through its overexpression in ESCC.