Cdc20 inhibitor apcin inhibits the growth and invasion of osteosarcoma cells

Gao, Yuan; Zhang, Benyuan; Wang, Yuming; Shang, Guanning

doi:10.3892/or.2018.6467

Cited by 36 publications

(30 citation statements)

References 52 publications

(70 reference statements)

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“…CDC20 regulates cell cycle and was recognized as an oncogenic role in tumorigenesis and tumor progression. Overexpression of CDC20 was reported in various malignancies (27). CDC20 was detected to be upregulated in pancreatic ductal adenocarcinoma (PDAC), and overexpression of CDC20 was associated with poor differentiation and lower RFS of PDAC patients (28).…”

Section: Discussionmentioning

confidence: 99%

Overexpression of ASPM, CDC20, and TTK Confer a Poorer Prognosis in Breast Cancer Identified by Gene Co-expression Network Analysis

et al. 2019

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Breast cancer is one of the most common malignancies among females, and its prognosis is affected by a complex network of gene interactions. In this study, we constructed free-scale gene co-expression networks using weighted gene co-expression network analysis (WGCNA). The gene expression profiles of GSE25055 were downloaded from the Gene Expression Omnibus (GEO) database to identify potential biomarkers associated with breast cancer progression. GSE42568 was downloaded for validation. A total of 9 modules were established via the average linkage hierarchical clustering. We identified 3 hub genes (ASPM, CDC20, and TTK) in the significant module ( R 2 = 0.52), which were significantly correlated with poor prognosis both in test and validation datasets. In the datasets GSE25055 and GSE42568, higher expression levels of ASPM, CDC20, and TTK correlated with advanced tumor grades. Immunohistochemistry data from the Human Protein Atlas also demonstrated that their protein levels were higher in tumor samples. According to gene set enrichment analysis, 4 commonly enriched pathways were identified: cell cycle pathway, DNA replication pathway, homologous recombination pathway, and P53 signaling pathway. In addition, strong correlations were found among their expression levels. In conclusion, our WGCNA analysis identified candidate prognostic biomarkers for further basic and clinical researches.

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Section: Discussionmentioning

confidence: 99%

Overexpression of ASPM, CDC20, and TTK Confer a Poorer Prognosis in Breast Cancer Identified by Gene Co-expression Network Analysis

et al. 2019

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“…Indeed, silencing of CDC20 using RNA interference in pancreatic cells lines augmented cytotoxicity when exposed to chemotherapies [ 41 ]. Furthermore, use of the pharmacological agents APCIN or pro-TAME, which inhibit the binding of CDC20 to the APC (and thus APC CDC20 formation) resulted in increased apoptosis and death in multiple cancer cell lines, indicating that inhibition of the APC may be a useful anticancer approach [ 42 – 44 ]. Moreover, an interesting recent study showed that cancer cells displaying chromosome cohesion defects were synthetically lethal with APC subunit depletion, providing further evidence that APC inhibition may be a powerful means to killing cancer cells [ 45 ].…”

Section: The Anaphase Promoting Complex (Apc) and Cancer Development mentioning

confidence: 99%

The role of Anaphase Promoting Complex activation, inhibition and substrates in cancer development and progression

VanGenderen

Harkness

Arnason

2020

Aging

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The Anaphase Promoting Complex (APC), a multi-subunit ubiquitin ligase, facilitates mitotic and G1 progression, and is now recognized to play a role in maintaining genomic stability. Many APC substrates have been observed overexpressed in multiple cancer types, such as CDC20, the Aurora A and B kinases, and Forkhead box M1 (FOXM1), suggesting APC activity is important for cell health. We performed BioGRID analyses of the APC coactivators CDC20 and CDH1, which revealed that at least 69 proteins serve as APC substrates, with 60 of them identified as playing a role in tumor promotion and 9 involved in tumor suppression. While these substrates and their association with malignancies have been studied in isolation, the possibility exists that generalized APC dysfunction could result in the inappropriate stabilization of multiple APC targets, thereby changing tumor behavior and treatment responsiveness. It is also possible that the APC itself plays a crucial role in tumorigenesis through its regulation of mitotic progression. In this review the connections between APC activity and dysregulation will be discussed with regards to cell cycle dysfunction and chromosome instability in cancer, along with the individual roles that the accumulation of various APC substrates may play in cancer progression.

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“…Furthermore, apcin, as a specific CDC20 inhibitor, was used to further evaluate the role of CDC20 in radiosensitivity. Apcin is a specific inhibitor with direct action against the APC Cdc20 complex, which occupies the D-box binding pocket within the WD40 domain to block the connection between CDC20 and APC, thereby regulating the activity of its downstream substrates and exerting its biological functions [ 25 , 26 ]. As shown in Figure 2 H, apcin (10 μM) pretreatment plus gamma-ray radiation had significantly greater inhibitory effects on cell viability than radiation exposure alone.…”

Section: Resultsmentioning

confidence: 99%

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

Gao

Wen

Chen

et al. 2020

IJMS

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Radiotherapy is an important modality for the local control of human cancers, but the radioresistance induced by aberrant apoptotic signaling is a hallmark of cancers. Restoring the aberrant apoptotic pathways is an emerging strategy for cancer radiotherapy. In this study, we determined that targeting cell division cycle 20 (CDC20) radiosensitized colorectal cancer (CRC) cells through mitochondrial-dependent apoptotic signaling. CDC20 was overexpressed in CRC cells and upregulated after radiation. Inhibiting CDC20 activities genetically or pharmacologically suppressed the proliferation and increased radiation-induced DNA damage and intrinsic apoptosis in CRC cells. Mechanistically, knockdown of CDC20 suppressed the expression of antiapoptotic protein Mcl-1 but not other Bcl-2 family proteins. The expressions of CDC20 and Mcl-1 respond to radiation simultaneously through direct interaction, as evidenced by immunoprecipitation and glutathione S-transferase (GST) pull-down assays. Subsequently, decreased Mcl-1 expression inhibited the expression level of phosphorylated checkpoint kinase 1 (p-Chk1), thereby resulting in impaired DNA damage repair through downregulating the homologous recombination repair protein Rad51 and finally causing apoptotic signaling. In addition, both CDC20 and Chk1 inhibitors together, through in vivo studies, confirmed the radiosensitizing effect of CDC20 via inhibiting Mcl-1 and p-Chk1 expression. In summary, our results indicate that targeting CDC20 is a promising strategy to improve cancer radiotherapy.

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Cdc20 inhibitor apcin inhibits the growth and invasion of osteosarcoma cells

Cited by 36 publications

References 52 publications

Overexpression of ASPM, CDC20, and TTK Confer a Poorer Prognosis in Breast Cancer Identified by Gene Co-expression Network Analysis

Overexpression of ASPM, CDC20, and TTK Confer a Poorer Prognosis in Breast Cancer Identified by Gene Co-expression Network Analysis

The role of Anaphase Promoting Complex activation, inhibition and substrates in cancer development and progression

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

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