PBK/TOPK: An Effective Drug Target with Diverse Therapeutic Potential

Abstract

T-lymphokine-activated killer cell-originated protein kinase (TOPK, also known as PDZ-binding kinase or PBK) plays a crucial role in cell cycle regulation and mitotic progression. Abnormal overexpression or activation of TOPK has been observed in many cancers, including colorectal cancer, triple-negative breast cancer, and melanoma, and it is associated with increased development, dissemination, and poor clinical outcomes and prognosis in cancer. Moreover, TOPK phosphorylates p38, JNK, ERK, and AKT, which are involved in many cellular functions, and participates in the activation of multiple signaling pathways related to MAPK, PI3K/PTEN/AKT, and NOTCH1; thus, the direct or indirect interactions of TOPK make it a highly attractive yet elusive target for cancer therapy. Small molecule inhibitors targeting TOPK have shown great therapeutic potential in the treatment of cancer both in vitro and in vivo, even in combination with chemotherapy or radiotherapy. Therefore, targeting TOPK could be an important approach for cancer prevention and therapy. Thus, the purpose of the present review was to consider and analyze the role of TOPK as a drug target in cancer therapy and describe the recent findings related to its role in tumor development. Moreover, this review provides an overview of the current progress in the discovery and development of TOPK inhibitors, considering future clinical applications.

High expression of PDZ-binding kinase is correlated with poor prognosis and immune infiltrates in hepatocellular carcinoma

“…T-lymphokine-activated killer-cell-originated protein kinase (TOPK), also known as PDZ-binding kinase (PBK), is a novel mitotic serine/threonine protein kinase, which was confirmed to be associated with the development, progression, and metastasis of malignancies and to be a potential therapeutic target in cancer therapy [ 30 ]. Studies have shown that PBK expression is increased in various cancers compared with normal tissues [ 31 ]. In this study, we explored the expression of PBK in pan-cancers using oncomine and TIMER databases.…”

PBK/TOPK Inhibitor Suppresses the Progression of Prolactinomas

“…TOPK may promote the occurrence and development of In addition, we also found that HI-TOPK-032 could inhibit the phosphorylation of p38 MAPK. TOPK, as a serine-threonine kinase, belongs to the MAPKK family and is closely associated with a variety of biological activities (47). TOPK has been reported to play a role in the cell cycle regulation and mitosis process and become active during mitosis to phosphorylate Thr9 residues of CCNB1/CDK1 (48).…”

Alterations of Chromatin Regulators in the Pathogenesis of Urinary Bladder Urothelial Carcinoma

“…This non-concordance may be explained by differences between individual molecular subtypes, especially in the case of FOXA1 , which directs luminal differentiation. These genes in addition comprise PBK (encoding a protein kinase also known as TOPK with a broad spectrum of targets, including histones [ 121 ]) and HJURP , encoding a chaperone for centromeric variant histones. Intriguingly, a sole publication on bladder cancer so far implicates HJURP in the regulation of PPARγ and SIRT1 [ 122 ].…”