Role of aurora kinase B in regulating resistance to paclitaxel in breast cancer cells

Aurora kinase B (AURKB) is a type of functional kinase with primary functions of participating in cell mitosis, which has been identified to be involved in the occurrence and development of malignant tumors strongly. However, it still remains a controversial with respect to the relationship between...

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Bibliographic Details
Published in:Human cell : official journal of Human Cell Research Society 2022-03, Vol.35 (2), p.678-693
Main Authors: Liu, Min, Li, Yinan, Zhang, Cui, Zhang, Qing
Format: Article
Language:English
Subjects:
Animals
Aurora kinase
Aurora Kinase B - genetics
Aurora Kinase B - metabolism
Biomedical and Life Sciences
Breast cancer
Breast Neoplasms - drug therapy
Breast Neoplasms - genetics
Cell Biology
Cytoplasm
Drug resistance
Female
Gene regulation
Gynecology
Humans
Kinases
Life Sciences
Localization
Mitosis
Oncology
Paclitaxel
Paclitaxel - pharmacology
Phosphorylation
Proteins
Reproductive Medicine
Research Article
RNA, Small Interfering
siRNA
Spatial discrimination
Stem Cells
Surgery
Transcription
Tumors
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Summary:Aurora kinase B (AURKB) is a type of functional kinase with primary functions of participating in cell mitosis, which has been identified to be involved in the occurrence and development of malignant tumors strongly. However, it still remains a controversial with respect to the relationship between the phosphorylation level of AURKB and its function. In our initial research, there was no significant difference in the relative content of AURKB protein between drug-resistant breast cancer cells and wild-type cells; however, its phosphorylation level in drug-resistant cells was significantly higher than that in wild-type cells. Subsequent cell and animal experiments both confirmed the positive correlation between AURKB phosphorylation and drug resistance. Furthermore, PRKCE in the upstream was identified to regulate the phosphorylation of AURKB, which promoted the change of spatial localization of AURKB from nucleus to cytoplasm. Accordingly, phosphorylated AURKB reduced the negative regulation of downstream RAB27B transcription physically, and interacted with RAB27B in cytoplasm to maintain its protein stability. Eventually, it promoted exosome secretion of drug-resistant cells and drug efflux. Using shRNA to knockdown AURKB expression, using hesperadin to inhibit AURKB activity, mutating the AURKB phosphorylation site, or using siRNA as well as BIM to inhibit the activity of the upstream AURKB phosphorylation regulatory protein PRKCE, all of which directly or indirectly reduce AURKB phosphorylation, are effective in reversing PTX resistance in cells. Collectively, this study provides experimental evidence for PRKCE/AURKB/RAB27B axis in regulating the resistance to paclitaxel (PTX) in breast cancer cells, offering a potential intervention target for reversing drug resistance.
ISSN:1749-0774
0914-7470
1749-0774
DOI:10.1007/s13577-022-00675-8