Posted: Monday, July 18, 2022
Overexpression of the cell division cycle 20 homologue (CDC20) may impair clinical outcomes for patients with hematologic malignancies, according to Samantha Bruno, MD, of the University of Bologna and Institute of Hematology, Italy, and colleagues. In fact, excessive CDC20 levels are associated with a poor clinical prognosis for patients with multiple myeloma and lymphoma, including overall survival. The findings of this article were published in the Journal of Experimental & Clinical Cancer Research.
“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,” stated the study authors.
CDC20 is well known to be involved in the correct segregation of chromosomes during mitosis, but recent research suggests CDC20 may also be involved in regulating apoptosis and immune cell infiltration. The Biological General Repository for Interaction Data Sets indicates that CDC20 has approximately 800 physical interactions via proteomic analyses, and these interactors are involved in several different cell-cycle phases. Overexpression of CDC20 in cancer cells has been linked to expression of several interactors, most notably cell-cycle regulators such as APC/CCDC20 substrates.
Multiple myeloma cells are susceptible to unstable chromosomal segregation and aneuploidy. Further, multiple myeloma cell lines exhibit overexpression of CDC20 but low levels of spindle assembly checkpoint components such as AURKC, PLK2, and PLK3. High-risk patients with multiple myeloma exhibit high levels of the CDC20 transcript as well as decreases in CDH1, the combination of which is associated with enhanced cancer cell proliferation. Preclinical research using multiple myeloma cell lines indicates that knockdown of CDC20 may be associated with an increase in the APC/CCDC20 substrate, which may improve cancer cell growth arrest. Lastly, high levels of CDC20 were associated with inferior overall survival in TT2 and HM cohorts.
Disclosure: For full disclosures of the study authors, visit jeccr.biomedcentral.com.