Critical roles of LGN/GPSM2 phosphorylation by PBK/TOPK in cell division of breast cancer cells

Fukukawa, Chikako; Ueda, Koji; Nishidate, Toshihiko; Katagiri, Toyomasa; Nakamura, Yusuke

doi:10.1002/gcc.20795

Cited by 49 publications

(47 citation statements)

References 27 publications

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“…Besides, many human cancer-associated viruses also express constitutively active viral GPCRs [44]. As previous reported, GNAI1 can suppresses tumor cell migration and invasion [45], GPSM2 may influence the cell division in cancer [46], and GNAO1 is demonstrated to play an important role in oncogenesis [47]. Combination with these findings, we speculate that G-protein coupled receptor protein signaling pathway may play an important role in RCC initiation, and these genes are suspected to participate in the process of RCC through involved in this pathway.…”

Section: Discussionmentioning

confidence: 80%

Identification of Key Genes and Pathways in Renal Cell Carcinoma Through Expression Profiling Data

Liu

Wang

Sun

2015

Kidney Blood Press Res

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Background/Aims: To isolate key genes and pathways in renal cell carcinoma (RCC), which might reveal more evidences on the regulation network and contribute to pathogenic mechanisms of RCC. Methods: Microarray data of GSE34676, GSE23926 and GSE48008 were downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) and differentially expressed miRNAs were respectively screened using Limma package, followed by the selection of CNV associated genes and miRNAs. A multi-molecular regulation interaction network was constructed, and significant modules were subsequently isolated from the network by Molecular Complex Detection (Mcode) of Cytoscape. Finally, GO terms and KEGG pathways of these genes and miRNAs in significant modules were enriched using DAVID. Results: Total 403 DEGs and 231 differentially expressed miRNAs were screened in RCC samples and normal group. Moreover, 1369 genes and 68 miRNAs were isolated by CNV analysis. Besides, a total of 59 miRNAs and 209 genes that related to 340 interaction pairs were analyzed and used to construct the network and 2 significant modules were identified. In the modules, CAV1 and CAV2 were shown to correlate with RCC. GNAI1, GPSM2 and GNAO1 were likely involved in the regulation of RCC through G protein signal transduction. Besides, G-protein coupled receptor protein signaling pathway, focal adhesion, MAPK signaling pathway and neuroactive ligand receptor interaction were enriched. Conclusion: Our study suggests that several crucial genes including CAV1,CAV2, GNAI1, GPSM2, and GNAO1 and pathways may play key roles in RCC progression.

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Section: Discussionmentioning

confidence: 80%

Identification of Key Genes and Pathways in Renal Cell Carcinoma Through Expression Profiling Data

Liu

Wang

Sun

2015

Kidney Blood Press Res

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“…PBK is a serine/threonine protein kinase related to the mitogen-activated protein kinase kinase (MAPKK) family. Overexpression of this gene has been implicated in tumorigenesis [17, 28]. Moreover, the cyclin kinase subunit CKS2 was upregulated; CKS2 expression was increased in several types of cancer and associated with tumor progression [29, 30].…”

Section: Discussionmentioning

confidence: 99%

PSMB8 and PBK as potential gastric cancer subtype-specific biomarkers associated with prognosis

et al. 2016

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Gastric adenocarcinoma is a common form of cancer associated with a poor prognosis. We analyzed microarray profiling data from 48 patients with gastric adenocarcinoma to characterize gastric cancer subtypes and identify biomarkers associated with prognosis. We identified two major subtypes of gastric adenocarcinoma differentially associated with overall survival (P = 0.025). Genes that were differentially expressed were identified using specific criteria (P < 0.001 and >1.5-fold); expression of 294 and 116 genes was enriched in good and poor prognosis subtypes, respectively. Genes related to translational elongation and cell cycle were upregulated in the poor prognosis group. Of these genes, upregulation of proteasome subunit beta type 8 PSMB8 and PDZ binding kinase PBK was confirmed by real-time reverse transcription-PCR analysis. PSMB8 or PBK knockdown had no effect on gastric cancer cell proliferation but suppressed cell migration and invasion, respectively. Furthermore, immunohistochemistry analysis of 385 gastric cancer patients revealed that increased nuclear expression of PSMB8 and PBK was correlated with depth of invasion, lymph node metastasis, and lower survival rates. Taken together, two gastric adenocarcinoma subtypes were predictive of prognosis. PSMB8 and PBK were predictive of gastric cancer prognosis and could be potential gastric cancer subtype-specific biomarkers.

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“…PBK has been identified as a kinase regulating mitosis by phosphorylation of GPSM2 (G-protein signaling modulator 2) in breast cancer cells [33]. PBK also interacts with p53 to regulate expression of cell cycle genes [8].…”

Section: Discussionmentioning

confidence: 99%

PBK/TOPK mediates geranylgeranylation signaling for breast cancer cell proliferation

et al. 2015

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PDZ binding-kinase (PBK) (also named T-lymphokine-activated killer cell-originated protein kinase (TOPK)), a serine/threonine kinase, is tightly controlled in normal tissues but elevated in many tumors, and functions in tumorigenesis and metastasis. However, the signaling that regulates expression of PBK in cancer cells remains elusive. Here we show that atorvastatin (Lipitor), an inhibitor of hydroxymethylglutaryl co-enzyme A (HMG-CoA) reductase that is a rate-limiting enzyme of mevalonate pathway, down-regulates expression of PBK by impairing protein geranylgeranylation. The shRNA knockdown demonstrated that Yes-associated protein (YAP) mediates geranylgeranylation-regulated expression of PBK. Importantly, atorvastatin or the geranylgeranyltransferase I inhibitor GGTI-298 inhibited breast cancer cell proliferation through inactivation of YAP signaling and down-regulation of PBK. These findings have defined a new signaling pathway that regulated expression of PBK and identified PBK as a downstream target of the Hippo-YAP signaling, uncoverd a mechanism underlying the anti-cancer effect by inhibition of mevalonate pathway and geranylgeranylation, and provided a potential target for breast cancer targeted therapy.

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Critical roles of LGN/GPSM2 phosphorylation by PBK/TOPK in cell division of breast cancer cells

Cited by 49 publications

References 27 publications

Identification of Key Genes and Pathways in Renal Cell Carcinoma Through Expression Profiling Data

Identification of Key Genes and Pathways in Renal Cell Carcinoma Through Expression Profiling Data

PSMB8 and PBK as potential gastric cancer subtype-specific biomarkers associated with prognosis

PBK/TOPK mediates geranylgeranylation signaling for breast cancer cell proliferation

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