Polo-Like Kinase 4 (PLK4) Is Overexpressed in Central Nervous System Neuroblastoma (CNS-NB)

Bailey, Anders W.; Suri, Amreena; Chou, Pauline M.; Pundy, Tatiana; Gadd, Samantha; Raimondi, Stacey L.; Tomita, Tadanori; Sredni, Simone Treiger

doi:10.3390/bioengineering5040096

Cited by 21 publications

(21 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Polo‐like kinases are important regulators in cell cycle and DNA damage response, which are shown to be closely related to pathogenesis of cancers. In vitro study reports that PLK4 promotes tumor cell proliferation, survival, invasion, and migration in central nervous system neuroblastoma and increases tumor growth . And in pancreatic cancer, the inhibitor of PLK4 results in a significant reduction of tumor initiating cells .…”

Section: Discussionmentioning

confidence: 99%

Polo‐like kinase 4 correlates with greater tumor size, lymph node metastasis and confers poor survival in non‐small cell lung cancer

Zhou

Fan

Dong

2019

Clinical Laboratory Analysis

View full text Add to dashboard Cite

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractBackground: Our study aimed to investigate the association of polo-like kinase 4 (PLK4) expression with tumor features as well as survival in non-small cell lung cancer (NSCLC) patients.Methods: Five hundred and sixty NSCLC patients who underwent pulmonary resection were recruited, and their tumor specimens were obtained. Immunohistochemistry (IHC) staining was performed to assess PLK4 expression in tumor specimen. Follow-up documents were reviewed, and the disease-free survival (DFS) and overall survival (OS) were evaluated.Results: According to IHC staining, there were 277 (49.5%) patients with PLK4 low expression and 283 (50.5%) patients with PLK4 high expression. PLK4 high expression was further classified into three different classes: high+, high++, high+++, and 122 (21.8%), 127 (22.7%), 34 (6.1%) patients were with PLK4 high+, high++, high+++ expression, respectively. Polo-like kinase 4 expression was correlated with larger tumor size, LYN metastasis, and higher TNM stage. As for survival, DFS and OS were lower in patients with PLK4 high expression compared with patients with PLK4 low expression. In addition, DFS and OS were the lowest in patients with PLK4 high+++ expression, followed by those with PLK4 high++ expression, PLK4 high+ expression, and then patients with PLK4 low expression. Univariate and multivariate Cox's proportional hazard regression model analyses further disclosed that PLK4 was an independent predictive factor for poor DFS and OS in NSCLC patients. Conclusion:Our study preliminarily illuminates the clinical implication of PLK4 in NSCLC, while further studies are still needed to explicit the value of PLK4 in surveillance and treatment of NSCLC. K E Y W O R D Sdisease-free survival, non-small cell lung cancer, overall survival, polo-like kinase 4, tumor features

show abstract

Section: Discussionmentioning

confidence: 99%

Polo‐like kinase 4 correlates with greater tumor size, lymph node metastasis and confers poor survival in non‐small cell lung cancer

Zhou

Fan

Dong

2019

Clinical Laboratory Analysis

View full text Add to dashboard Cite

show abstract

“…PLK4 has also been recognized as a promising therapeutic target for numerous tumors 29 . Moreover, previous studies determined that PLK4 level was upregulated in NB, and the deficiency of PLK4 weakened NB aggressive progression 30,31 . Here, we first identified that PLK4 is a functionally important target of miR‐513c‐5p in regulating malignant NB cell progression in vitro.…”

Section: Discussionmentioning

confidence: 77%

“…29 Moreover, previous studies determined that PLK4 level was upregulated in NB, and the deficiency of PLK4 weakened NB aggressive progression. 30,31 Here, we first identified that PLK4 is a functionally important target of miR-513c-5p in regulating malignant NB cell progression in vitro. Furthermore, we showed that DLX6-AS1 functioned as a posttranscriptional regulator of PLK4 expression by sponging miR-513c-5p.…”

Section: Discussionmentioning

confidence: 99%

Silencing of long non‐coding RNADLX6‐AS1 weakens neuroblastoma progression by the miR‐513c‐5p/PLK4 axis

et al. 2020

View full text Add to dashboard Cite

Emerging evidence has demonstrated the crucial roles of long noncoding RNAs in human cancers, including neuroblastoma (NB). DLX6 antisense RNA 1 (DLX6-AS1) has been identified as an oncogenic driver in NB. However, the mechanisms of DLX6-AS1 in NB progression are not fully understood. Our data showed that DLX6-AS1 was significantly overexpressed in NB tissues and cells. Moreover, DLX6-AS1 silencing repressed NB cell viability, colony formation, migration, and invasion, and promoted cell cycle arrest and apoptosis in vitro, as well as decreased tumor growth in vivo. Mechanistically, DLX6-AS1 operated as a miR-513c-5p sponge. MiR-513c-5p mediated the regulation of DLX6-AS1 on NB cell malignant progression in vitro. PLK4 was a target of miR-513c-5p-and DLX6-AS1-controlled PLK4 expression via sponging miR-513c-5p. Furthermore, the suppressive effect of miR-513c-5p overexpression on NB cell malignant progression in vitro was reversed by PLK4 upregulation. Our findings identified a novel regulatory mechanism, the DLX6-AS1/miR-513c-5p/PLK4 axis, in NB progression, highlighting a strong rationale for developing DLX6-AS1 as a new target for NB management.

show abstract

“…All told, the targeting of PLK4 appears to be a promising new anticancer strategy. As to childhood cancers, PLK4 has been reported to be overexpressed in patient-derived rhabdoid tumour and neuroblastoma samples (Sredni et al 2017b ; Tian et al 2018 ; Bailey et al 2018 ). Moreover, PLK4i have been shown to exert anticancer activities against cultured rhabdoid tumour, medulloblastoma and neuroblastoma cells (Sredni et al 2017a , b ; Suri et al 2019 ; Tian et al 2018 ), but they have not yet been tested in ES cells.…”

Section: Introductionmentioning

confidence: 99%

Anticancer effects of the PLK4 inhibitors CFI-400945 and centrinone in Ewing’s sarcoma cells

Kerschner-Morales

Kühne

Becker

et al. 2020

J Cancer Res Clin Oncol

View full text Add to dashboard Cite

Purpose Polo-like kinase 4 (PLK4) inhibitors, such as CFI-400945 and centrinone, are emerging as promising antineoplastic agents. However, their effectiveness against Ewing’s sarcoma, a highly aggressive childhood cancer, remains to be established. Methods CFI-400945 and centrinone were tested in three Ewing’s sarcoma cell lines with different TP53 status. Effects were assessed by flow-cytometric analyses of cell death, dissipation of the mitochondrial transmembrane potential and cell cycle distribution, by cell viability assay as well as by caspase 3/7 activity measurement, by immunoblotting and by immunofluorescence microscopy. Results CFI-400945 and centrinone elicited cell death in p53 wild-type and mutant Ewing’s sarcoma cells. Both agents induced mitochondrial membrane depolarisation, caspase 3/7 activation, PARP1 cleavage and DNA fragmentation, indicating an apoptotic form of cell death. In addition, the PLK4 inhibitors induced a G2/M cell cycle arrest, particularly when cell killing was attenuated by the pan-caspase inhibitor z-VAD-fmk. Moreover, CFI-400945 treatment produced polyploidy. Conclusion Our findings show that PLK4 inhibitors were effective against Ewing’s sarcoma cells in vitro and thus provide a rationale for their evaluation in vivo.

show abstract

Polo-Like Kinase 4 (PLK4) Is Overexpressed in Central Nervous System Neuroblastoma (CNS-NB)

Cited by 21 publications

References 65 publications

Polo‐like kinase 4 correlates with greater tumor size, lymph node metastasis and confers poor survival in non‐small cell lung cancer

Polo‐like kinase 4 correlates with greater tumor size, lymph node metastasis and confers poor survival in non‐small cell lung cancer

Silencing of long non‐coding RNADLX6‐AS1 weakens neuroblastoma progression by the miR‐513c‐5p/PLK4 axis

Anticancer effects of the PLK4 inhibitors CFI-400945 and centrinone in Ewing’s sarcoma cells

Contact Info

Product

Resources

About