A kind of functional kinase called aurora kinase B (AURKB) participates primarily in cell mitosis and has been significantly linked to the emergence and progression of malignant tumors. Regarding the connection between AURKB's amount of phosphorylation and its function, there is still some debate.
In our initial study, there was no discernible difference between drug-resistant breast cancer cells and wild-type cells in terms of the relative quantity of the AURKB protein; nevertheless, the drug-resistant cells' levels of phosphorylation were noticeably greater than those of the wild-type cells. AURKB phosphorylation and drug resistance are positively correlated, as demonstrated by later cell and animal studies.
AURKB's phosphorylation was also controlled by PRKCE, which was shown to be upstream. This enhanced AURKB's transition from the nucleus to the cytoplasm. Thus, phosphorylated AURKB physically decreased the negative regulation of downstream RAB27B transcription and interacted with RAB27B in the cytoplasm to maintain the protein stability of that protein.
In the end, it encouraged drug efflux and exosome production from drug-resistant cells. Inhibiting the activity of the upstream AURKB phosphorylation regulatory protein PRKCE with siRNA and BIM is effective in reversing PTX resistance in cells, as is using shRNA to knockdown AURKB expression, hesperadin to inhibit AURKB activity, mutation of the AURKB phosphorylation site, or siRNA alone.
Collectively, this research offers experimental proof that the PRKCE/AURKB/RAB27B axis controls paclitaxel (PTX) resistance in breast cancer cells, suggesting a possible target for therapy to reverse drug resistance.
AURKB expression in breast cancer tissues and cells is abnormally high
AURKB was unusually strongly expressed in breast cancer tissues, according to the analysis of TCGA breast cancer data performed using the online program ACLBI (Fig. 1a). The relative amount of AURKB mRNA in breast cancer tissues was then shown to be considerably greater than that in the equivalent surrounding tissues when the clinical specimens were detected using quantitative PCR.
Similar to this, immuno-histochemical detection showed that the AURKB protein was comparatively substantially expressed in breast cancer tissues. The emphasis of further research was the expression of AURKB in breast cancer cells.
Quantitative PCR and Western blot analysis showed that the relative levels of AURKB mRNA and protein were significantly higher in immortalized normal breast epithelial cells than in non-triple-negative breast cancer cells (MCF-7, ZR-75-1), triple-negative breast cancer cells (MDA-MB-231 and BT549), and PTX-resistant MDA-MB-231/PTX and BT549/PTX cells.
Note: According to that theory, the Chemdiv Compound Collection has a library of potentially selective Aurora A kinase inhibitors. You may browse through aurora libraries that contain more than 10000 different compounds.
