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

Abstract

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.

Functional analysis of recurrent non-coding variants in human melanoma

“…Like TERT, CDC20 performs a variety of canonical and non-canonical functions, many of which can be implicated in cancer formation 49,52,58,59,[65][66][67][68][69][70][71] . Most crucial is its role in the cell cycle, where it interacts with the anaphase-promoting complex to degrade cyclin B and signal the end of metaphase and the start of anaphase 72 .…”

A novel ferroptosis-related gene prognostic index for prognosis and response to immunotherapy in patients with prostate cancer

“…Interestingly, a recent study demonstrated that E2F1-mediated transcription is essential for sphingosine-1-phosphate (S1P)-induced upregulation of PD-L1 expression ( 42 ), which may partly explain why FRGPI-high patients responded better to anti-PD-L1 than FRGPI-low patients in our study. Cell division cycle 20 (CDC20) acts as an anaphase-promoting complex activator that controls the proper segregation of chromosomes in mitosis ( 43 ). It was previously incorporated into several ferroptosis-related prognostic models in various tumors ( 44 , 45 ), but its specific functional role in ferroptosis has not been characterized.…”

Blood transcriptome analysis revealed the crosstalk between COVID-19 and HIV

“…Cyclin B1 (CCNB1) is a crucial mitosis initiator and controller ( 48 ). CDC20 is a well-known regulator of cell division, regulating chromosome segregation during mitosis ( 49 ). The mitotic chromosome condensation is established by topoisomerase IIα (TOP2A), a core component of mitotic chromosomes ( 50 ).…”