Analyses of expressions and prognostic values of Polo-like kinases in non-small cell lung cancer

Zeng, Yu; Li, Nanhong; Liu, Wang; Zeng, Mingqing; Cheng, Junfen; Huang, Jian

doi:10.1007/s00432-020-03288-6

Cited by 17 publications

(23 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There was a 3.3 ± 0.3 and 3.4 ± 0.6-fold increase in PLK1 expression in A549 and NCI-H460 cell lines, respectively, compared to the lung non-tumor cell line. These results are in concordance with previous studies that reported a PLK1 overexpression in NSCLC, highlighting the relevance of PLK1 targeting [28,29].…”

Section: Plk1 Is Upregulated In Lung Cancer Cellssupporting

confidence: 93%

Navitoclax Enhances the Therapeutic Effects of PLK1 Targeting on Lung Cancer Cells in 2D and 3D Culture Systems

et al. 2022

View full text Add to dashboard Cite

The efficacy of antimitotics is limited by slippage, whereby treated cells arrested in mitosis exit mitosis without cell division and, eventually, escape apoptosis, constituting a serious resistance mechanism to antimitotics. Strategies to overcome slippage should potentiate the cancer cell killing activity of these antimitotics. Such strategies should accelerate cell death in mitosis before slippage. Here, we undertook a mechanistic analysis to test whether the apoptosis activator Navitoclax potentiates apoptosis triggered by the antimitotic BI2536, a potent inhibitor of Polo-like kinase 1 (PLK1) with the goal of overcoming slippage. We found that cancer cells in 2D cultures treated with BI2536 alone accumulate in mitosis, but a significant fraction of arrested cells undergo slippage and survive. Remarkably, combining BI2536 with Navitoclax dramatically reduces slippage, shifting the cell fate to accelerated death in mitosis. The results are confirmed in 3D spheroids, a preclinical system that mimics in vivo tumor drug responses. Importantly, in 3D spheroids, the effect of the BI2536/Navitoclax combination requires a lower therapeutic dosage of each drug, underlying its potential to improve the therapeutic index. Our results highlight the relevance of apoptosis potentiators to circumvent slippage associated with antimitotics. The combination of BI2536 with Navitoclax shows in vitro synergy/additive effect, which warrants further clinical research.

show abstract

Section: Plk1 Is Upregulated In Lung Cancer Cellssupporting

confidence: 93%

Navitoclax Enhances the Therapeutic Effects of PLK1 Targeting on Lung Cancer Cells in 2D and 3D Culture Systems

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Pearson correlation analysis and mutual exclusivity analysis showed a remarkable positive correlation between PLK1 and PLK4. Zeng et al also found the same conclusion in human non-small cell lung cancer [ 30 ]. The cross talk of PLK1 with PLK4 needs to be further demonstrated.…”

Section: Discussionsupporting

confidence: 58%

Polo-like kinases as potential targets and PLK2 as a novel biomarker for the prognosis of human glioblastoma

Ding

Liu

Zhang

et al. 2022

Aging

View full text Add to dashboard Cite

The most prevalent malignant central nervous system (CNS) cancer is glioblastoma multiforme (GBM). PLKs (polo-like kinases) are a kind of serine-threonine kinase that modulate DNA replication, mitosis, and stress responses. PLKs in GBM need to be better studied and examined in terms of their expression, function, along with prognostic significance. Using an existing publicly available data set, we evaluated the expression level and prognostic relevance of PLKs in GBM patients at the molecular level. The biological processes along with cascades of the screened gene were predicted using the functional enrichment of Gene Set Enrichment Analysis, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathways. The data illustrated that PLK1/3/4 contents were greater in GBM tissues than in non-tumorous tissues, but PLK2/5 expression levels were lower. PLK2 expression was also linked to patient outcome in GBM. Our findings imply that PLKs might be useful molecular indicators as well as prospective treatment targets for GBM. A PLK2 inhibitor has been studied for the first time in a glioma cell in this work. In glioma cells, ON1231320 has anticancer effects. Finally, a summary of PLK inhibitors is presented, along with projections for future progress.

show abstract

“…CDC25C in the cytoplasm cannot activate the cyclin B1/CDK1 complex, resulting in the arrest of G2/M phase and the formation of PGCCs [8]. Phosphorylation of CDC25C at Ser198 by PLK1 and PLK3 promotes to the CDC25C nuclear translocation [13,43]. Ser216 of CDC25C can be phosphorylated by CHEK1 and CHK2 kinases, which promotes to the CDC25C nuclear output, and results in G2/M arrest of the cell cycle [8].…”

Section: Discussionmentioning

confidence: 99%

PLK4 is a key molecule in the formation of PGCCs and promotes invasion and migration of progeny cells derived from PGCCs

Fu¹,

Chen²,

Yang³

et al. 2022

J. Cancer

View full text Add to dashboard Cite

Purpose: Cancer stem cells (CSCs) are the evil source of tumor metastasis and recurrence. Polyploid giant cancer cells (PGCCs) that exhibit the characteristics of CSCs produced daughter cells via asymmetric division. The molecular mechanisms of daughter cells derived from PGCCs with high migration, invasion, and proliferation abilities in colorectal cancer (CRC) are explored in this paper based on the bioinformatics analysis. Materials and Methods: We characterized the expression of CSC-related genes in CRCs by analyzing the mRNAsi of The Cancer Genome Atlas and survival time. Weighted gene co-expression network analysis was performed to identify the modules of the hub and key genes. The migration, invasion, and proliferation abilities of cells, the expression of epithelial-mesenchymal transition (EMT)-related proteins and polo-like kinase 4 (PLK4) were compared in LoVo and Hct116 cells with and without bufalin treatment. In addition, the expression and subcellular location of cell division cycle 25C (CDC25C) in cells before and after PLK4 knockdown were assessed. Results: Eight hub genes were screened out and positively association with mRNAsi in CRCs based on bioinformatic analysis. Among them, checkpoint Kinase-1 (CHEK1), budding uninhibited by benzimidazoles 1 Homolog Beta (BUB1B) and PLK4 were closely associated with the prognosis of CRC patients. Bufalin could induce the formation of PGCCs in LoVo and Hct116 cell lines. PLK4 was overexpressed in PGCCs with progeny cells and progeny cells derived from PGCCs had strong migration and invasion abilities by expressing epithelial-mesenchymal transition (EMT)-related proteins. PLK4 could interact with CDC25C and promote CDC25C phosphorylation which was associated with the formation of PGCCs. Decreasing CDC25C expression in both LoVo and Hct116 PGCCs with progeny cells, while levels of pCDC25C-ser216 and pCDC25C-ser198 were increased in LoVo and decreased in Hct116 PGCCs with progeny cells. pCDC25C-ser216 located in the cytoplasm and pCDC25C-ser198 located in the nucleus in cells after bufalin treatment. Furthermore, expression of CDC25C, pCDC25C-ser216, and pCDC25C-ser198 was downregulated after PLK4 knockdown. Furthermore, the expression level of PLK4 was associated with differentiated degree, and lymph node metastasis in human CRC tissues. Conclusion: PLK4 contributes to the formation of PGCCs by regulating the expression of CDC25C and is associated with the expression and subcellular location of CDC25C, pCDC25C-ser216 and pCDC25C-ser198.

show abstract

Analyses of expressions and prognostic values of Polo-like kinases in non-small cell lung cancer

Cited by 17 publications

References 60 publications

Navitoclax Enhances the Therapeutic Effects of PLK1 Targeting on Lung Cancer Cells in 2D and 3D Culture Systems

Navitoclax Enhances the Therapeutic Effects of PLK1 Targeting on Lung Cancer Cells in 2D and 3D Culture Systems

Polo-like kinases as potential targets and PLK2 as a novel biomarker for the prognosis of human glioblastoma

PLK4 is a key molecule in the formation of PGCCs and promotes invasion and migration of progeny cells derived from PGCCs

Contact Info

Product

Resources

About