Home Blog of Signal Transduction Epigenetics Aurora Kinase Inhibition of Cdc20 suppresses the metastasis in triple negative breast cancer (TNBC)

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Inhibition of Cdc20 suppresses the metastasis in triple negative breast cancer (TNBC)

Background: Cdc20 is a crucial activator of the anaphase-promoting complex (APC/C) and is known to be essential in mitosis regulation. Abnormally high expression of Cdc20 has been reported in several malignancies. We aimed to study the Cdc20 expression in human breast cancer tissues, focusing specifically on Cdc20 in Triple-Negative Breast Cancer (TNBC).

Methods: The expression of mitotic regulators mRNA in three TNBC cell lines or three other breast cancer cell lines was determined by the RNA-sequencing database. 14,713 human breast cancer patient samples included in Breast Cancer-GenExminer v4.5 were used to analyze whether cell division cycle 20 (Cdc20) expression was related to TNBC. To find whether Cdc20 expression impacted prognosis in TNBC, we used 2,249 TNBC patients database. The loss of Cdc20 by RNA interference (shRNA) and several mitotic inhibitors including Apcin, ZM447439, BI 2536, and VX-680 on the capacities of proliferation, migration, invasion were evaluated by colony-forming, wound-healing, transwell assay, and western blot, respectively.

Results: We studied the mitosis-related genes and proteins that are closely related to TNBC through the National Center for Biotechnology Information (NCBI) database. We found that Cdc20, one of the central mitotic regulators, is significantly upregulated in human TNBC, and its expression level is positively correlated with metastasis-free and relapse-free patient survival. We also found Cdc20 is highly conserved in TNBC in comparison to other breast cancer subtype cell lines. Cdc20 deficiency results in a decrease in cell growth and migration in four TNBC cell lines. Also, several mitotic inhibitors, such as Apcin, VX-680, ZM447439, and BI 2536, blocked cancer cell growth and invasion.

Conclusions: These results suggest an essential role of Cdc20 in tumor formation and metastasis of TNBC, which might be a potential target therapy for TNBC treatment.

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S1048 Tozasertib (VX-680) Tozasertib (VX-680) is a pan-Aurora inhibitor, mostly against Aurora A with Kiapp of 0.6 nM in a cell-free assay, less potent towards Aurora B/Aurora C and 100-fold more selective for Aurora A than 55 other kinases. The only exceptions are Fms-related tyrosine kinase-3 (FLT-3) and BCR-ABL tyrosine kinase, which are inhibited by the Tozasertib with both Ki of 30 nM. Tozasertib induces apoptosis and autophagy. Phase 2.

Related Targets

Aurora Kinase FLT3 Autophagy Bcr-Abl