Identification of CDK2 as a Novel Target in Treatment of Prostate Cancer

Yin, Xifeng; Yu, Jun; Zhou, Yang; Wang, Chengyue; Jiao, Zhimin; Qian, Zhounan; Sun, Hao; Chen, Binghai

doi:10.2217/fon-2017-0561

Cited by 41 publications

(19 citation statements)

References 29 publications

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“…Many studies have suggested that CDK2 could be a crucial factor in the progression of cancer by regulating several pathways and might be a prospective biomarker and indicator of prognosis. Therefore, CDK2 and its cyclin binding partners are possible therapeutic targets for future cancer treatments (Yin et al, 2018;Zhang et al, 2018;Wood et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Integrative Bioinformatics Approaches to Map Potential Novel Genes and Pathways Involved in Ovarian Cancer

Kumar

Siva

et al. 2019

Front. Bioeng. Biotechnol.

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Background and aims: Ovarian cancer (OC) is the seventh most commonly detected cancer among women. This study aimed to map the hub and core genes and potential pathways that might be involved in the molecular pathogenesis of OC. Methods: In the present work, we analyzed a microarray dataset (GSE126519) from the Gene Expression Omnibus (GEO) database and used the GEO2R tool to screen OC cells and ovarian SINE-resistant cancer cells for differentially expressed genes (DEGs). For the functional annotation of the DEGs, we conducted Gene Ontology (GO) and pathway enrichment analyses (KEGG) using the DAVID v6.8 online server and GenoGo Metacore TM , Cortellis Solution software. Protein-protein interaction (PPI) networks were constructed using the STRING database, and Cytoscape software was used for visualization. The survival analysis was performed using the online platform GEPIA2 to determine the prognostic value of the expression of hub genes in cell lines from OC patients. Results: We identified a total of 809 upregulated and 700 downregulated DEGs. GO analysis revealed that the genes with statistically significant differences in expression were mainly associated with biological processes involved in the cell cycle, the mitotic cell cycle, mitotic nuclear division, organ morphogenesis, cell development, and cell morphogenesis. By using the Analyze Networks (AN) algorithm in GeneGo, we identified the most relevant biological networks involving DEGs that were mainly enriched in the cell cycle (in metaphase checkpoints) and revealed the role of APC in cell cycle regulation pathways. We found 10 hub genes and four core genes (FZD6, FZD8, CDK2, and RBBP8) that are strongly linked to OC. Conclusion: This study sheds light on the molecular pathogenesis of OC and is expected to provide potential molecular biomarkers that are beneficial for the treatment and clinical molecular diagnosis of OC.

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Section: Discussionmentioning

confidence: 99%

Integrative Bioinformatics Approaches to Map Potential Novel Genes and Pathways Involved in Ovarian Cancer

Kumar

Siva

et al. 2019

Front. Bioeng. Biotechnol.

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“…Interestingly, CDKs are known to be upregulated during cancer and CDK inhibitors are used as anticancer drug trial (Goel et al 2018;J. H. Jeong et al 2009;Yin et al 2018;Malumbres and Barbacid 2009;Vijayaraghavan et al 2018). As a result, finding mangiferin targeting CDK4 as anticancer drug target has validated our approach (Figure 2).…”

Section: Discussionmentioning

confidence: 62%

CDK4 as a phytochemical based anticancer drug target

Chando¹,

Hussain²,

Rana

et al. 2019

Preprint

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Success story of plant-based medicine had been overlooked during the advent of modern pharmaceutical industry. Despite the negligence of the multimillion-dollar drug industry, people entirely rely on medicinal plants in some part of the world. In this study, we have emphasized on going back to those traditional medicinal practices to figure out their underlying mechanism to move forward on phytochemical based drug development. We screened Medicinal Plant Database Bangladesh 1.0 (MPDB1.0) and on-going extension, MPDB2.0, of that database to find traditionally used medicinal plants and their active compounds. Here, Mangiferin, extracted from Mangifera indica, have been demonstrated to interact with cell cycle regulator Cyclin-dependent Kinase 4 (CDK4). CDK4 is differentially expressed during Glioblastoma multiforme (GBM), Brain Lower Grade Glioma (LGG), and Sarcoma (SARC). Expression of CDK4 is interlinked to the patients' survival rate and its consistent expression throughout different stages have provided the advantage to use it as diagnostic tool and drug target. Altogether, this study demonstrated that simple mango tree extracted active compounds, mangiferin, can work as potential anticancer drug and leveraging the recent advancement of sequencing and gene expression data can accelerate the phytochemical based drug discovery process.

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“…CDKs are known to regulate cell-cycle phases and the overexpression of CDKs can induce cell proliferation (38,39). A previous study showed that inhibition of CDK2 suppressed PCa metastases by inactivating PI3K/Akt signaling (40). CDK5, CDK6, CDK7, and CDK9 can suppress CRPC through AR inactivation (41)(42)(43)(44).…”

Section: Discussionmentioning

confidence: 99%

Characterization of Kinase Expression Related to Increased Migration of PC-3M Cells Using Global Comparative Phosphoproteome Analysis

Gao

Kwon

et al. 2020

Cancer Genomics Proteomics

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Background/Aim: Prostate cancer (PCa) is the second-most commonly occurring cancer among men, worldwide. Although the mechanisms associated with the progression of castration-resistant prostate cancer (CRPC) have been widely studied, the mechanism associated with more distant metastases from the bone remains unknown. This study aimed to characterize potential pathogenic kinases associated with highly metastatic PCa, that may regulate phosphorylation in extensively involved and diverse signaling pathways that are associated with the development of various cancers. Materials and Methods: A mass spectrometry (MS)based comparative phosphoproteome strategy was utilized to identify differentially expressed kinases between the highly aggressive PCa cell-lines PC-3 and PC-3M. Results: Among 2,968 phosphorylation sites in PCa cells, 151 differently expressed phosphoproteins were identified. Seven motifs:-SP- ,-SxxE- ,-PxS- ,-PxSP- ,-SxxK- ,-SPxK-, and-SxxxxxP-were found to be highly expressed in PC-3M cells. Based on these motifs, the kinases p21-activated kinase (PAK)2, Ste20-like kinase (SLK), mammalian Ste20-like kinase (MST)4, mitogenactivated kinase kinase (MAP2K)2, and A-Raf proto-oncogene serine/threonine kinase (ARAF) were up-regulated in PC-3M cells. Conclusion: PAK2, SLK, MST4, MAP2K2, and ARAF are kinases that are potentially associated with the progression of increased migration in PC-3M cells and may represent molecule regulators or drug targets for highly metastatic PCa therapy. Prostate cancer (PCa) is the second-most commonly occurring cancer among men, worldwide (1, 2). According to the latest report by the American Cancer Society, in 2020, 191,930 new cases of PCa will be diagnosed and 33,330 individuals will die from PCa, in the United States (3). Unlike other types of cancers, PCa grows very slowly and may not cause symptoms for years, until the cancer cells metastasize out of the prostate, developing to advanced PCa (4, 5). This characteristic has limited most cases of PCa being recognized and treated during the early stages, and prostate-specific antigen technology began to be applied to the detection of primary-stage PCa in 1994 (6, 7). Because PCa is an androgen-dependent disease (8), androgen deprivation therapy is the standard therapy for the initial stages of advanced PCa; however, treatment can eventually result in the development of castration-resistant PCa (CRPC) (9). Androgen receptor (AR) inhibition remains a key factor in CRPC therapies. Metastatic CRPC (mCRPC) develops when PCa cells spread to other parts of the body, where they can grow and spread, even under medical treatment (10). According to the "seed and soil" theory, proposed by Paget (11), PCa spreads in the bloodstream as "seeds", which settle in specific organs, which represent 543 This article is freely accessible online.

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Identification of CDK2 as a Novel Target in Treatment of Prostate Cancer

Abstract: These data indicated that CDK2 was a crucial factor in metastasis of Pca and might be a novel therapy target. [Formula: see text].

Cited by 41 publications

References 29 publications

Integrative Bioinformatics Approaches to Map Potential Novel Genes and Pathways Involved in Ovarian Cancer

Integrative Bioinformatics Approaches to Map Potential Novel Genes and Pathways Involved in Ovarian Cancer

CDK4 as a phytochemical based anticancer drug target

Characterization of Kinase Expression Related to Increased Migration of PC-3M Cells Using Global Comparative Phosphoproteome Analysis

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