Characterization of a MAPKK-like protein kinase TOPK

Matsumoto, Suguru; Abe, Yasuhito; Fujibuchi, Taketsugu; Takeuchi, Takashi; Kito, Katsumi; Ueda, Norifumi; Shigemoto, Kazuhiro; Gyo, Kiyofumi

doi:10.1016/j.bbrc.2004.10.133

Cited by 98 publications

(127 citation statements)

References 21 publications

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“…PBK/TOPK was initially identified as a mitotic protein kinase (27), assisting the recruitment of cylcin-dependent kinase 1 (CDK1)/cyclin B to mitotic spindles, where PBK/TOPK plays a role in the formation of the spindle midzone and cytokinesis (10). Previous studies have identified various oncogenic functions of PBK/TOPK related to multiple signaling pathways such as the MAPK pathway (14), PI3K/AKT pathway (8,28,29) and p53 pathway (13,15).…”

Section: Discussionmentioning

confidence: 99%

“…Physiologically, PBK/TOPK plays a positive regulatory role in proper chromosomal separation and cytokinesis through phosphorylation of various targets (10,11). PBK/TOPK gene expression is regulated by the cell-cycle-specific transcription factors E2F and cAMPresponsive element binding/activating transcription factor (CREB/ATF) (12).…”

Section: Overexpression Of Pbk/topk Contributes To Tumor Development mentioning

confidence: 99%

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

Ohashi

Komatsu

Ichikawa

et al. 2016

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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

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Section: Discussionmentioning

confidence: 99%

Section: Overexpression Of Pbk/topk Contributes To Tumor Development mentioning

confidence: 99%

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

Ohashi

Komatsu

Ichikawa

et al. 2016

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“…Cellcycle-specific regulation of PBK/TOPK is mediated partly by transcription factors E2F and CREB/ATF (Nandi and Rapoport, 2006). Previous studies also suggest a role for PBK/TOPK in cytokinesis and DNA damage sensing and repair through phosphorylation of histone H2AX (Matsumoto et al, 2004;Zykova et al, 2006;Ayllo´n and O'Connor, 2007).…”

Section: Introductionmentioning

confidence: 94%

PBK/TOPK interacts with the DBD domain of tumor suppressor p53 and modulates expression of transcriptional targets including p21

et al. 2010

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“…TOPK is a 322 amino-acid MAPKK-like serine/threonine kinase and is highly expressed in various types of cancer, such as lymphoma, leukemia, breast cancer, melanoma and colorectal cancers, but is undetectable in normal tissues except the germ cells of testis and several fetal tissues (Abe et al, 2000;Simons-Evelyn et al, 2001;Nandi et al, 2004;Park et al, 2006;Zykova et al, 2006;Zhu et al, 2007). In cultured cells, the expression of TOPK is upregulated during mitosis, when it is thought to be phosphorylated on Thr 9 and activated by cyclin B1/cdk1 (Matsumoto et al, 2004). Because it enhances cyclin B1/cdk1-dependent phosphorylation of PRC1, TOPK has been hypothesized to have a role in cytokinesis Chen et al, 2009b).…”

Section: Introductionmentioning

confidence: 99%

TOPK/PBK promotes cell migration via modulation of the PI3K/PTEN/AKT pathway and is associated with poor prognosis in lung cancer

et al. 2011

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We integrated four gene expression profile data sets, namely two different pair-matched stage I lung adenocarcinoma data sets, secondary metastatic tumors vs benign tumors and lung tumor metastasizes to the brain, and we identified one kinase, T-LAK Cell-Originated Protein Kinase (TOPK), as a putative gene that promotes metastasis. To delineate the role of TOPK in lung cancer, we showed that overexpression of TOPK, but not a catalytically inactive form of TOPK, can enhance the migration and invasion of lung fibroblasts or cells with low TOPK expression. In addition, TOPK-induced cell migration was shown to be a PI3K/AKT-dependent event. TOPK concurrently promoted AKT phosphorylation at Ser 473 and decreased the phosphatase and tensin homolog (PTEN) levels, whereas TOPK knockdown had the reverse effects. LY294002, a PI3K inhibitor, did not inhibit the TOPK-induced decrease in PTEN, and coexpression of PTEN significantly reduced TOPK-induced AKT phosphorylation in a dose-dependent manner; these results indicate that the TOPK-mediated PTEN decrease has an upstream role in regulating PI3K/AKT-stimulated migration. Using immunohistochemical analysis of lung cancer tissue samples, we showed that a high TOPK expression level correlates strongly with reduced overall and disease-free survivals. Moreover, an inverse correlation between TOPK and PTEN expression was present and is consistent with the biochemical findings. Finally, a combination of high TOPK and low PTEN expression was inversely correlated with overall and disease-free survivals, independent of other pathologic staging factors. Our results suggest that TOPK is a potential therapeutic target in lung cancer that promotes cell migration by modulating a PI3K/PTEN/AKT-dependent signaling pathway; they also suggest that high TOPK expression, either alone or in combination with a low level of PTEN, may serve as a prognostic marker for lung cancer.

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Characterization of a MAPKK-like protein kinase TOPK

Cited by 98 publications

References 21 publications

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

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

PBK/TOPK interacts with the DBD domain of tumor suppressor p53 and modulates expression of transcriptional targets including p21

TOPK/PBK promotes cell migration via modulation of the PI3K/PTEN/AKT pathway and is associated with poor prognosis in lung cancer

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