Silencing of polo-like kinase 2 increases cell proliferation and decreases apoptosis in SGC-7901 gastric cancer cells

Liu, Li Ying; Wang, Wei; Zhao, Ling; Guo, Bo; Yang, Juan; Zhao, Xiao Ge; Song, Tu Sheng; Huang, Chen; Xu, Jianrong

doi:10.3892/mmr.2014.3077

Cited by 11 publications

(13 citation statements)

References 28 publications

(36 reference statements)

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“…The above studies demonstrate the tumor‐promoting role of PLK2. However, many other studies have indicated that it is a tumor suppressor . In agreement with previous studies, PLK2 inhibition promoted cell cycle progression and cell proliferation in normal culture Saos2 cells, indicating its role as a suppressor.…”

Section: Discussionsupporting

confidence: 90%

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PLK2 phosphorylates and inhibits enriched TAp73 in human osteosarcoma cells

Liao

et al. 2015

Cancer Medicine

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TAp73, a member of the p53 tumor suppressor family, can substitute for p53 function, especially in p53‐null and p53‐mutant cells. However, TAp73 enrichment and phosphorylation change its transcriptional activity. Previously, we found that the antitumor function of TAp73 was reactivated by dephosphorylation. Polo‐like kinase 2 (PLK2) plays an important role in bone development. Using a biological information database and phosphorylation prediction software, we hypothesized that PLK2 phosphorylates TAp73 and inhibits TAp73 function in osteosarcomas. Actually,we determined that PLK2 physically binds to and phosphorylates TAp73 when TAp73 protein abundance is up‐regulated by cisplatin. PLK2‐phosphorylated TAp73 at residue Ser48 within the TA domain; phosphorylation of TAp73 was abolished by mutating this residue. Moreover, PLK2 inhibition combined with cisplatin treatment in osteosarcoma Saos2 cells up‐regulated p21 and puma mRNA expression to a greater extent than cisplatin treatment alone. Inhibiting PLK2 in TAp73‐enriched Saos2 cells resulted in inhibited cell proliferation, increased apoptosis, G1 phase arrest, and decreased cell invasion. However, these changes did not occur in TAp73 knockdown Saos2 cells. In conclusion, these findings reveal a novel PLK2 function in the phosphorylation of TAp73, which prevents TAp73 activity in osteosarcoma cells. Thereby, this research provides an insight into the clinical treatment of malignant tumors overexpressing TAp73.

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Section: Discussionsupporting

confidence: 90%

“…it is a tumor suppressor [66,67]. In agreement with previous studies, PLK2 inhibition promoted cell cycle progression and cell proliferation in normal culture Saos2 cells, indicating its role as a suppressor.…”

Section: (A) (B)supporting

confidence: 92%

PLK2 phosphorylates and inhibits enriched TAp73 in human osteosarcoma cells

Liao

et al. 2015

Cancer Medicine

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“…Methylated PLK2 was shown to be predictive of OS, with cases with a PFS of less than 12 months showing the highest levels compared with the remainder of the cohort. Our data showing the relationship between PLK2 drug induced apoptosis are supported by Liu et al [18] who showed that PLK2 silenced gastric carcinoma cells were resistant to apoptosis, showing reduced levels of caspase-3 protein. The authors also provided evidence for PLK2 as a tumour suppressor, since gastric carcinoma cells showed a significantly enhanced growth rate when transfected with PLK2 SiRNA.…”

Section: Discussionsupporting

confidence: 86%

Methylated PLK2 is a prognostic biomarker in taxane-treated breast cancers

Chivers

Lattanzio²,

Garrone³

et al. 2020

DCC

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Background: In search of potential biomarkers of drug responsiveness the tumour suppressor PLK2 has been identified as a mediator of taxane sensitivity in some tumour types, based on its role of G2M checkpoint regulation.Objective: The current study set out to evaluate PLK2 methylation in breast cancer treated with neo-adjuvant chemotherapy including a taxane, as a biomarker of disease progression.Methods: Silencing of PLK2 in MCF-7 cells followed by taxane treatment was assessed using apoptotic readout for proof of principle. DNA was extracted from 64 cases of diagnostic surgical FFPE sections. Using pyrosequencing, levels of PLK2 promoter methylation were measured.Results: Silencing of PLK2 resulted in a significantly reduced apoptotic response following paclitaxel treatment (compared with scramble transfected controls). An association with higher levels of CpG island promoter methylation was seen for those cases with a progression-free survival (PFS) of less than 12 months. Kaplan-Meier analysis showed there was an association between overall survival (OS) and level of methylation (p = .06).Conclusions: Thus, based on data obtained from this pilot study, further larger studies evaluating the utility of PLK2 methylation as a potential predictive biomarker in breast cancer are warranted.

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“…This accounts for glioblastoma [ 168 ], hepatocellular carcinoma [ 169 ], acute myeloid leukemia [ 170 ], and for B-cell malignancies [ 171 ] where PLK2 is epigenetically silenced, as well as for cervical cancer where PLK2 exhibits anti-proliferative and apoptosis-promoting effects [ 172 ]. This accounts for gastric cancer, too, according to siRNA-mediated PLK2 knockdown [ 173 ]. In breast cancer, reduced PLK2 expression is linked to adverse prognosis [ 174 ].…”

Section: Plks and Tumor Developmentmentioning

confidence: 99%

Modelling the Functions of Polo-Like Kinases in Mice and Their Applications as Cancer Targets with a Special Focus on Ovarian Cancer

Kressin

Fietz

Becker

et al. 2021

Cells

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Polo-like kinases (PLKs) belong to a five-membered family of highly conserved serine/threonine kinases (PLK1-5) that play differentiated and essential roles as key mitotic kinases and cell cycle regulators and with this in proliferation and cellular growth. Besides, evidence is accumulating for complex and vital non-mitotic functions of PLKs. Dysregulation of PLKs is widely associated with tumorigenesis and by this, PLKs have gained increasing significance as attractive targets in cancer with diagnostic, prognostic and therapeutic potential. PLK1 has proved to have strong clinical relevance as it was found to be over-expressed in different cancer types and linked to poor patient prognosis. Targeting the diverse functions of PLKs (tumor suppressor, oncogenic) are currently at the center of numerous investigations in particular with the inhibition of PLK1 and PLK4, respectively in multiple cancer trials. Functions of PLKs and the effects of their inhibition have been extensively studied in cancer cell culture models but information is rare on how these drugs affect benign tissues and organs. As a step further towards clinical application as cancer targets, mouse models therefore play a central role. Modelling PLK function in animal models, e.g., by gene disruption or by treatment with small molecule PLK inhibitors offers promising possibilities to unveil the biological significance of PLKs in cancer maintenance and progression and give important information on PLKs’ applicability as cancer targets. In this review we aim at summarizing the approaches of modelling PLK function in mice so far with a special glimpse on the significance of PLKs in ovarian cancer and of orthotopic cancer models used in this fatal malignancy.

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Silencing of polo-like kinase 2 increases cell proliferation and decreases apoptosis in SGC-7901 gastric cancer cells

Cited by 11 publications

References 28 publications

PLK2 phosphorylates and inhibits enriched TAp73 in human osteosarcoma cells

PLK2 phosphorylates and inhibits enriched TAp73 in human osteosarcoma cells

Methylated PLK2 is a prognostic biomarker in taxane-treated breast cancers

Modelling the Functions of Polo-Like Kinases in Mice and Their Applications as Cancer Targets with a Special Focus on Ovarian Cancer

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