Molecular interactions of polo-like kinase 1 in human cancers

Shin, Joo‐Shik; Roberts, Tara L.; Wang, Bin; Lee, Cheok Soon

doi:10.1136/jclinpath-2016-203656

Cited by 26 publications

(29 citation statements)

References 90 publications

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“…Of these target genes, FOXM1 and PLK1 are both critical proteins necessary for the initiation of mitosis or M phase 19, 20 . Due to their strong role in mitotic entry, both are found upregulated in many cancers 21, 22 . To identify the role of PGRB in the promotion of mitosis, RNA transcript levels of known mitotic-initiating proteins were evaluated.…”

Section: Resultsmentioning

confidence: 99%

“…This work provided further detailed analysis of PGR binding directly at the loci of mitosis- promoting genes: Foxm1 , Plk1 , Cdc25c , and Cdk1 . Since PLK1 and FOXM1 are necessary for cell cycle progression 19 , they have consistently been identified to be expressed in a variety of cancers 21, 22 . PLK1 alone is found upregulated in human ovarian cancer 49, 50 , endometrial carcinoma 51 , ectopic endometriosis 52 , and breast cancer 53 , often correlating with increased proliferation and severity.…”

Section: Discussionmentioning

confidence: 99%

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Constitutive Expression of the Progesterone Receptor Isoforms Promotes Hormone-Dependent Development of Ovarian Neoplasms

Wetendorf

et al. 2019

Preprint

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30Abnormal expression of the progesterone receptor (PGR) isoforms, PGRA and PGRB, is 31 often observed in women with reproductive tract cancer. To assess the importance of the PGR 32 isoform ratio in the maintenance of the healthy reproductive tract, mice with Cre recombinase-33 activated PGRA and PGRB transgenes were bred with the PGR Cre mouse model to generate 34 strains expressing either PGRA or PGRB in PGR positive tissues. The PGRB mice developed 35 ovarian neoplasms at 23 weeks of age derived from ovarian luteal cells, while the PGRA 36 expressing mice displayed a reduced frequency of tumor development. Transcriptomic analyses 37 of the ovarian tumors revealed an enhanced AKT pathway signature, which is in agreement with 38 expression changes found in human ovarian adenocarcinoma. Effective treatment with the PGR 39 antagonist RU486 reduced tumor growth and the expression of cell cycle genes. We concluded 40 that tumor growth and proliferation is hormone and PGR isoform dependent. Further analysis of 41 the PGRB cistrome identified binding events of critical mitotic phase entry genes. This work 42 suggests an intriguing mechanism whereby the expression of the PGR isoforms determines in 43 vivo neoplasia through high-jacking of the cell cycle pathway. 44 45 Proper functioning of the reproductive tract depends on the appropriate signaling and 46 expression of the hormone receptors and their ligands for pregnancy and the maintenance of a 47 healthy fertile state 1 . Disruption of hormone signaling not only results in infertility and 48 miscarriage, but also can lead to diseases such as leiomyoma, endometriosis, and reproductive 49 tract cancer 2 . Endometrial cancer and ovarian cancer collectively contribute to over 37,000 50 deaths per year in the United States 3 . Further understanding of hormone signaling in the 51 reproductive tract, especially as it relates to the initiation and progression of disease, can 52 accelerate the development of specialized therapies to treat these diseases and cancers. 53 The ovary produces the female steroid hormones, estrogen and progesterone under the 54 direction from gonadotropins secreted from the pituitary gland 1 . These hormones function by 55 binding to their cognate receptors, the estrogen and progesterone receptors, to elicit activation or 56 repression of their respective target genes. The progesterone receptor (PGR) is expressed in all 57 uterine compartments, yet is limited to the pre-ovulatory granulosa cells of the ovary 4 . PGR 58 function is further regulated through the unique expression of different isoforms 5,6 . Genetically 59 engineered mice have been generated with specific ablation of both isoforms: PGRAKO and 60 PGRBKO. Phenotypic analysis of these mice demonstrated that the PGRA isoform is critical for 61 female mouse fertility. The PGRBKO mice were fertile with normal ovulation and embryo 62 implantation, yet displayed a mammary gland phenotype of altered ductal epithelial 63 proliferation 7 . The only uterine phenotype attributed to the PGRB...

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Constitutive Expression of the Progesterone Receptor Isoforms Promotes Hormone-Dependent Development of Ovarian Neoplasms

Wetendorf

et al. 2019

Preprint

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“…In order to complete this study, we chose to silence the biologically relevant endogenous polo like kinase 1 gene (Plk1) upregulated in many cancers. [24,25] This gene is implicated in cell cycle progression and its downregulation induces apoptosis. [26,27] Silencing of the expression of Plk1 by RNA interference with siPlk1 can be assessed directly by measuring the cell viability, as compared to delivery with control siRNA.…”

Section: Silencing Of a Gene Of Therapeutic Interestmentioning

confidence: 99%

Design and evaluation of ionizable peptide amphiphiles for siRNA delivery

Neuberg

Wagner

Rémy

et al. 2019

International Journal of Pharmaceutics

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Small interfering RNAs (siRNAs) can down-regulate the expression of a target mRNA molecule in a sequence-specific manner, making them an attractive new class of drugs with broad potential for the treatment of diverse human diseases. Here, we report the synthesis of a series of cationic amphiphiles which were obtained by the coupling of amino acids and dipeptides onto a lipidic double chain. The new amphiphiles presenting a peptidic motif on a short hydrophilic spacer group were evaluated for selective gene silencing through RNA interference. Our results show that tryptophan residues boost siRNA delivery in an unexpected manner. The silencing experiments performed with very low concentrations of siRNA showed that the best formulations could induce significant death of tumor cells after silencing of polo-like kinase 1 which is implicated in cell cycle progression. In addition, these Trp containing peptide amphiphiles were highly efficient siRNA delivery vectors even in presence of competing serum proteins.3

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“…The expression of MAP9 is downregulated in colorectal cancer, whereas AURKA and Plk1 are upregulated (Rouquier et al, 2014). Dysregulation of AURKA and Plk1 are strongly associated with tumorigenesis (Weng Ng et al, 2016;Al-Khafaji et al, 2017;Chen et al, 2017;Zhu et al, 2017), and AURKA polymorphisms have also been reported in association with GC and breast cancer (Lopez-Cortes et al, 2018;Mesic et al, 2017). Considering the direct interactions of MAP9 with AURKA and Plk1, we believe that MAP9 plays key role in carcinogenesis.…”

Section: Discussionmentioning

confidence: 83%

MAP9 single nucleotide polymorphism rs1058992 is a risk of EBV-associated gastric carcinoma in Chinese population

Liu¹,

Xiao²,

Wu³

et al. 2018

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Microtubule-associated protein 9 (MAP9) is a mitosis-associated protein involved in bipolar spindle assembly. Following DNA damage, MAP9 stabilizes p53 via p300 and MDM2 (mouse double minute-2 homolog). The dysregulation of MAP9 was considered to be associated with tumorigenesis. Single nucleotide polymorphisms (SNPs) in key genes governing mitosis may particularly increase susceptibility to gastric carcinoma (GC). Our study demonstrated that the CC homozygous genotype of SNP rs1058992 located in the MAP9 gene was significantly correlated with EBV-associated GC (EBVaGC) in a recessive genetic model (OR = 2.558, 95% CI = 1.306-5.010, P = 0.043), and the C allele frequency of rs1058992 also showed significant correlation with EBVaGC (OR = 1.904, 95% CI = 1.141-3.179, P = 0.013). These results suggest that the MAP9 rs1058992 polymorphism is associated with risk of EBVaGC. The conversion of lysine to arginine caused by rs1058992 may affect development of EBVaGC; however, further studies in larger populations are needed to fully elucidate its role in EBVaGC.

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Molecular interactions of polo-like kinase 1 in human cancers

Cited by 26 publications

References 90 publications

Constitutive Expression of the Progesterone Receptor Isoforms Promotes Hormone-Dependent Development of Ovarian Neoplasms

Constitutive Expression of the Progesterone Receptor Isoforms Promotes Hormone-Dependent Development of Ovarian Neoplasms

Design and evaluation of ionizable peptide amphiphiles for siRNA delivery

MAP9 single nucleotide polymorphism rs1058992 is a risk of EBV-associated gastric carcinoma in Chinese population

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