Abstract
Breast cancer is a leading cause of death among women worldwide due to therapeutic resistance and cancer recurrence. Cancer stem cells are believed to be responsible for resistance and recurrence. Many efforts to overcome resistance and recurrence by regulating cancer stem cells are ongoing. Bub1 (Budding uninhibited by benzimidazoles 1) is a mitotic checkpoint serine/threonine kinase that plays an important role in chromosome segregation. Bub1 expression is correlated with a poor clinical prognosis in patients with breast cancer. We identified that depleting Bub1 using shRNAs reduces cancer stem cell potential of the MDA-MB-231 breast cancer cell line, resulting in inhibited formation of xenografts in immunocompromised mice. These results suggest that Bub1 may be associated with cancer stem cell potential and could be a target for developing anti-breast cancer stem cell therapies.
Highlights
Breast cancer is a leading cause of death among women worldwide due to therapeutic resistance and cancer recurrence
CD44 cooperates with HA-mediated motility (RHAMM or CD168) to deliver signals from extracellular HA, which is overexpressed in many advanced cancers including breast cancer[20,21,22,23]
cancer stem cell (CSC) are maintained by Aurora kinase A (AurA) and inhibiting AurA has been viewed as effective approach to target the CSC population in various cancers[31,32,33]
Summary
Breast cancer is a leading cause of death among women worldwide due to therapeutic resistance and cancer recurrence. Many efforts to overcome resistance and recurrence by regulating cancer stem cells are ongoing. We identified that depleting Bub[1] using shRNAs reduces cancer stem cell potential of the MDA-MB-231 breast cancer cell line, resulting in inhibited formation of xenografts in immunocompromised mice. Mitosis plays important roles balancing stem cells between self-renewal and differentiation to progenitor cells by regulating symmetric and asymmetric division[27,28]. These proteins have been shown to play an important role maintaining the CSC population and could be a potential therapeutic target for CSC-targeted therapies. Besides the involvement of mitotic kinases and mitotic checkpoint proteins in the maintenance of CSCs, genomic instability and polyploidy, which are induced by defects in mitotic kinases or mitotic checkpoint proteins, contribute to generating cancer-stem-like cells[35,36]
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