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

Abstract

Abstract. Background: PDZ-binding kinase/T-celloriginated 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 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.Esophageal cancer is the eighth most common cancer in the world (1) and esophageal squamous cell carcinoma (ESCC) accounts for 90% of esophageal carcinomas diagnosed in Asian countries. Although surgical techniques and perioperative management have progressed, ESCC remains one of the most aggressive carcinomas of the gastrointestinal tract. Since finding molecular targets for ESCC treatment might help improve the survival of patients with this lethal disease, studies have attempted to identify biological factors involved in the malignant potential of ESCC. However, few genes have been demonstrated to be associated with biological or pathological features of ESCC, suggesting that novel genes associated with the progression of ESCC need to be identified.Because identifying molecular targets for ESCC treatment may contribute to the improvement of survival of patients with this lethal disease, several recent studies have clarified that certain molecules, such as cyclo-oxygenase 2 (COX2), B-cell lymphoma (BCL2), tumor protein P53 (TP53), p16, cyclin D1, FAS, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and E-cadherin (2-6), have important roles in tumorigenesis and the development of ESCC. Moreover, various genetic and epigenetic alterations that contribute to the carcinogenesis of ESCC have been elucidated. In clinical settings, however, only a few molecules have been validated as diagnostic, therapeutic, or prognostic biomarkers for ESCC. These findings prompted us to further search for novel cancerassociated molecules.PDZ binding kinase/T-LAK cell originated protein kinase (PBK/TOPK) encodes a serine/threonine protein kinase and is 6457

PDZ binding kinase, regulated by FoxM1, enhances malignant phenotype via activation of β-Catenin signaling in hepatocellular carcinoma

“…Deregulation of PBK has been reported in other cancer types. Ohashi et al reported that PBK was up-regulated in esophageal squamous cell carcinoma and associated with worse prognosis [ 16 ]. Kwon et al showed that PBK expression in gastric carcinoma was significantly increased and predicted poor overall survival [ 17 ].…”

T-LAK cell-originated protein kinase (TOPK): an emerging target for cancer-specific therapeutics

“…Patients with combination of high TOPK and mutp53 had lowest prognosis 63 Haematological Primary AML qRT-PCR, immunoblotting TOPK detected in 9/12 samples; 3/3 ALL samples and in plasmocytoma and blastic type mantle cell lymphoma. Weak expression in peripheral blood stem cells 64 Gastric Gastric carcinoma IHC, immunoblotting Expression independently correlated with poor outcome 65 Oesophageal Oesophageal squamous cell carcinoma qRT-PCR, IHC, immunoblotting Expression independently correlated with poor outcome 66 Colorectal Colorectal carcinoma IHC tissue microarray No relationship between VEGFa gene amplification and TOPK expression/gene status 67 Expression of TOPK in primary tumours is linked to enhanced tumour aggression, invasion and metastatic spread in a variety of cancers. Multivariate analysis of clinical samples from numerous sites indicates that a significant relationship exists between TOPK expression in tumour tissue and poor prognosis for patients.…”

Acetylshikonin suppressed growth of colorectal tumour tissue and cells by inhibiting the intracellular kinase, T‐lymphokine‐activated killer cell‐originated protein kinase.

“…Because of the heterogenous nature of colorectal cancer, interventions in a range of oncogenic signalling pathways would be a rational approach for developing new therapies. One of the emerging oncogenic signalling molecules is an intracellular protein kinase, the T‐lymphokine‐activated killer cell‐originated protein kinase (TOPK; also known as PDZ binding kinase, PBK), which has been implicated in the development and progression of gastric (Ohashi et al, 2017) and ovarian cancers (Ikeda et al, 2016), oesophageal squamous cell carcinomas (Ohashi et al, 2016), and colorectal cancer (Zlobec et al, 2010).…”