Downregulation of CDC20 Increases Radiosensitivity through Mcl-1/p-Chk1-Mediated DNA Damage and Apoptosis in Tumor Cells

Gao, Yang; Wen, Pengbo; Chen, Bin; Hu, Guanshuo; Wu, Lijun; Xu, An; Zhao, Guoping

doi:10.3390/ijms21186692

Cited by 14 publications

(12 citation statements)

References 43 publications

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“…CDC20 has been also involved in the apoptotic response, by regulating phosphatidylcholine (PC) cycle [ 102 , 103 ] and balancing the activity of anti-apoptotic factors, as MCL-1 [ 104 – 108 ] and BCL-2 [ 108 , 109 ], and pro-apoptotic factors, as BIM [ 110 ] (Fig. 5 A-D).…”

Section: Main Textmentioning

confidence: 99%

CDC20 in and out of mitosis: a prognostic factor and therapeutic target in hematological malignancies

Bruno

Rorà

Napolitano

et al. 2022

J Exp Clin Cancer Res

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Cell division cycle 20 homologue (CDC20) is a well-known regulator of cell cycle, as it controls the correct segregation of chromosomes during mitosis. Many studies have focused on the biological role of CDC20 in cancer development, as alterations of its functionality have been linked to genomic instability and evidence demonstrated that high CDC20 expression levels are associated with poor overall survival in solid cancers. More recently, novel CDC20 functions have been demonstrated or suggested, including the regulation of apoptosis and stemness properties and a correlation with immune cell infiltration. Here, we here summarize and discuss the role of CDC20 inside and outside mitosis, starting from its network of interacting proteins. In the last years, CDC20 has also attracted more interest in the blood cancer field, being overexpressed and showing an association with prognosis both in myeloid and lymphoid malignancies. Preclinical findings showed that selective CDC20 and APC/CCDC20/APC/CCDH1 inhibitors, namely Apcin and proTAME, are effective against lymphoma and multiple myeloma cells, resulting in mitotic arrest and apoptosis and synergizing with clinically-relevant drugs. The evidence and hypothesis presented in this review provide the input for further biological and chemical studies aiming to dissect novel potential CDC20 roles and targeting strategies in hematological malignancies.

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Section: Main Textmentioning

confidence: 99%

CDC20 in and out of mitosis: a prognostic factor and therapeutic target in hematological malignancies

Bruno

Rorà

Napolitano

et al. 2022

J Exp Clin Cancer Res

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“…Importantly, recent studies have reported a group of specific inhibitors of Cdc20 in the pre-clinical model of different kinds of cancer ( 27 , 28 ). The tumor xenografts in immune-competent mice with or without CDC20 knockdown were shown to have a dramatic shrinkage in tumor volume, compared with the knockdown of CDC20 in the immune-deficient mice model as previous reproted ( 29 ). As CDC20 expression correlated with CAFs and MDSCs, it is proposed that the anti-tumor effects of targeting Cdc20 could be augmented by the immune system.…”

Section: Discussionmentioning

confidence: 75%

The Oncogenic Role of APC/C Activator Protein Cdc20 by an Integrated Pan-Cancer Analysis in Human Tumors

Sun

Chen

et al. 2021

Front. Oncol.

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The landscape of CDC20 gene expression and its biological impacts across different types of cancers remains largely unknown. Here, a pan-cancer analysis was performed to analyze the role of Cdc20 in various human cancers. Our results indicated that the expression levels of the CDC20 gene were significantly elevated in bladder cancer, breast cancer, colon cancer, rectum cancer, stomach cancer, esophageal cancer, head and neck cancer, kidney cancer, liver cancer, lung cancer, prostate cancer, pancreatic cancer, and uterine cancer. In addition, the expression of CDC20 was significantly and positively correlated with the increase of clinical stages in multiple cancer types, including breast cancer, kidney cancer, and lung cancer, et al. Among 33 cancer subtypes in the TCGA dataset, the high expression of CDC20 was correlated with poor prognosis in 10 cancer types. Furthermore, the abundance of phosphorylated Cdc20 in the primary tumor was elevated and correlated with increased tumor grade. Next, we sought to elucidate the oncogenic role by analyzing its association with immune infiltration. For most cancer types, the CDC20 expression was positively correlated with the infiltration of cancer-associated fibroblasts and myeloid-derived suppressor cells. To further understand its functional activity, we explored the classic Cdc20 downstream substrates, which were found to be mutually exclusive with the expression of Cdc20. Moreover, the pan-cancer analysis of the molecular function of Cdc20 indicated that BUB1, CCNA2, CCNB1, CDK1, MAD2L1, and PLK1 might play a critical role in interaction with Cdc20. The abundance of Cdc20 was further validated at transcriptional and translational levels with a publicly available dataset and clinical tumor tissues. The knockdown of Cdc20 dramatically inhibited tumor growth both in vivo and in vitro. Therefore, our studies delineated the oncogenic role of CDC20 and its prognostic significance at the pan-cancer level and proved its functional activity in Cdc20 high expression cancer types. Our studies will merits further molecular assays to understand the potential role of Cdc20 in tumorigenesis and provide the rationale for developing novel therapeutic strategies.

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“…Min Shi et al found that CDC20 played a crucial role in the development of hepatocellular carcinoma by regulating the PHD3 protein [ 26 ]. Besides, Yang Gao et al found that targeting CDC20 sensitized colorectal cancer cells to radiotherapy through mitochondrial-dependent apoptotic signaling [ 27 ]. Qin Zhang et al found that CDC20 combined with CD44 or β-catenin could serve as an important indicator for the prognosis of patients with prostate cancer [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

An integrated analysis of prognostic and immune infiltrates for hub genes as potential survival indicators in patients with lung adenocarcinoma

et al. 2022

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Objective Lung adenocarcinoma (LUAD) is one of the major subtypes of lung cancer that is associated with poor prognosis. The aim of this study was to identify useful biomarkers to enhance the treatment and diagnosis of LUAD. Methods GEO2R was used to identify common up-regulated differentially expressed genes (DEGs) in the GSE32863, GSE40791, and GSE75037 datasets. The DEGs were submitted to Metascape for gene ontology and pathway enrichment analysis as well as construction of the protein-protein interaction (PPI) network, while the molecular complex detection (MCODE) plug-in was employed to filter important subnetworks. The expression levels of the hub genes and their prognostic values were evaluated using the UALCAN, GEPIA2, and Kaplan-Meier plotter databases. The timer algorithm was utilized to determine the correlation between immune cell infiltration and the expression levels of hub genes in LUAD tissues. In addition, the hub gene mutation landscape and the correlation analysis with tumor mutational burden (TMB) score were evaluated using maftools package and ggstatsplot package in R software, respectively. Results We identified 156 common up-regulated DEGs, with gene ontology and pathway enrichment analysis indicating that they were mostly enriched in mitotic cell cycle process and cell cycle pathway. DEGs in the subnetwork with the largest number of genes were AURKB, CCNB2, CDC20, CDCA5, CDCA8, CENPF, and KNTC1. The seven hub genes were highly expressed in LUAD tissues and were associated with poor prognosis. These hub genes were negatively correlated with most immune cells. The somatic mutation landscape showed that AURKB, CDC20, CENPF, and KNTC1 had mutations and were positively correlated with TMB scores. Conclusions Our findings demonstrate that increased expression of seven hub genes is associated with poor prognosis for LUAD patients. Additionally, the TMB score indicates that the high expression of hub gene increases immune cell infiltration in patients with lung adenocarcinoma which may significantly improve response to immunotherapy.

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Downregulation of CDC20 Increases Radiosensitivity through Mcl-1/p-Chk1-Mediated DNA Damage and Apoptosis in Tumor Cells

Cited by 14 publications

References 43 publications

CDC20 in and out of mitosis: a prognostic factor and therapeutic target in hematological malignancies

CDC20 in and out of mitosis: a prognostic factor and therapeutic target in hematological malignancies

The Oncogenic Role of APC/C Activator Protein Cdc20 by an Integrated Pan-Cancer Analysis in Human Tumors

An integrated analysis of prognostic and immune infiltrates for hub genes as potential survival indicators in patients with lung adenocarcinoma

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