Proteomic profiling identifies upregulation of aurora kinases causing resistance to taxane-type chemotherapy in triple negative breast cancer
Abstract Nowadays, chemotherapy and immunotherapy remain the major treatment strategies for Triple-Negative Breast Cancer (TNBC). Identifying biomarkers to pre-select and subclassify TNBC patients with distinct chemotherapy responses is essential. In the current study, we performed an unbiased Rever...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-025-87315-x |
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| author | Bohan Ning Chang Liu Ali Cem Kucukdagli Jiuyi Zhang Han Jing Zhiqian Zhou Yuwei Zhang Ying Dong Yunjia Chen Hua Guo Jia Xu |
| author_facet | Bohan Ning Chang Liu Ali Cem Kucukdagli Jiuyi Zhang Han Jing Zhiqian Zhou Yuwei Zhang Ying Dong Yunjia Chen Hua Guo Jia Xu |
| author_sort | Bohan Ning |
| collection | DOAJ |
| description | Abstract Nowadays, chemotherapy and immunotherapy remain the major treatment strategies for Triple-Negative Breast Cancer (TNBC). Identifying biomarkers to pre-select and subclassify TNBC patients with distinct chemotherapy responses is essential. In the current study, we performed an unbiased Reverse Phase Protein Array (RPPA) on TNBC cells treated with chemotherapy compounds and found a leading significant increase of phosphor-AURKA/B/C, AURKA, AURKB, and PLK1, which fall into the mitotic kinase group. The increase of AURKA and AURKB protein was majorly due to a post-transcription level regulation, and Paclitaxel treatment induced Aurora Kinases protein phosphorylation on AURKA(T288)/AURKB(T232) sites and their protein stability. In our UAB TNBC cohort, the expression of AURKA and AURKB was significantly higher in TNBC tumors compared to normal adjacent tissues, and AURKB was found to be highly expressed in African American TNBC patients compared to European Americans. Moreover, Aurora Kinases overexpression in TNBC cells renders resistance to Paclitaxel treatment and attenuates the apoptosis effect triggered by chemotherapy treatment, suggesting Aurora Kinases could mediate the chemo-resistance in TNBC. Hence, a combination of Aurora kinase inhibitors or PROTAC degrader and taxane-type chemotherapy significantly enhanced the chemotherapy effect. In summary, we revealed that Aurora Kinases upregulation after treatment with chemotherapy could confer chemotherapy resistance to TNBC cells, and AURKB could serve as preselection markers for stratifying patients’ response to neoadjuvant chemotherapy. |
| format | Article |
| id | doaj-art-177e323fd18948c485b183d0d7ac10bd |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-177e323fd18948c485b183d0d7ac10bd2025-01-26T12:24:06ZengNature PortfolioScientific Reports2045-23222025-01-0115111510.1038/s41598-025-87315-xProteomic profiling identifies upregulation of aurora kinases causing resistance to taxane-type chemotherapy in triple negative breast cancerBohan Ning0Chang Liu1Ali Cem Kucukdagli2Jiuyi Zhang3Han Jing4Zhiqian Zhou5Yuwei Zhang6Ying Dong7Yunjia Chen8Hua Guo9Jia Xu10Department of Genetics, The University of Alabama at BirminghamDepartment of Genetics, The University of Alabama at BirminghamDepartment of Genetics, The University of Alabama at BirminghamDepartment of Genetics, The University of Alabama at BirminghamDepartment of Genetics, The University of Alabama at BirminghamDepartment of Genetics, The University of Alabama at BirminghamDepartment of Genetics, The University of Alabama at BirminghamDepartment of Pathology, Peking University First HospitalDepartment of Genetics, The University of Alabama at BirminghamDepartment of Pathology, Heersink School of Medicine, The University of Alabama at BirminghamDepartment of Genetics, The University of Alabama at BirminghamAbstract Nowadays, chemotherapy and immunotherapy remain the major treatment strategies for Triple-Negative Breast Cancer (TNBC). Identifying biomarkers to pre-select and subclassify TNBC patients with distinct chemotherapy responses is essential. In the current study, we performed an unbiased Reverse Phase Protein Array (RPPA) on TNBC cells treated with chemotherapy compounds and found a leading significant increase of phosphor-AURKA/B/C, AURKA, AURKB, and PLK1, which fall into the mitotic kinase group. The increase of AURKA and AURKB protein was majorly due to a post-transcription level regulation, and Paclitaxel treatment induced Aurora Kinases protein phosphorylation on AURKA(T288)/AURKB(T232) sites and their protein stability. In our UAB TNBC cohort, the expression of AURKA and AURKB was significantly higher in TNBC tumors compared to normal adjacent tissues, and AURKB was found to be highly expressed in African American TNBC patients compared to European Americans. Moreover, Aurora Kinases overexpression in TNBC cells renders resistance to Paclitaxel treatment and attenuates the apoptosis effect triggered by chemotherapy treatment, suggesting Aurora Kinases could mediate the chemo-resistance in TNBC. Hence, a combination of Aurora kinase inhibitors or PROTAC degrader and taxane-type chemotherapy significantly enhanced the chemotherapy effect. In summary, we revealed that Aurora Kinases upregulation after treatment with chemotherapy could confer chemotherapy resistance to TNBC cells, and AURKB could serve as preselection markers for stratifying patients’ response to neoadjuvant chemotherapy.https://doi.org/10.1038/s41598-025-87315-xTNBCCancer DisparityAURKAAURKBNeoadjuvant Chemotherapy |
| spellingShingle | Bohan Ning Chang Liu Ali Cem Kucukdagli Jiuyi Zhang Han Jing Zhiqian Zhou Yuwei Zhang Ying Dong Yunjia Chen Hua Guo Jia Xu Proteomic profiling identifies upregulation of aurora kinases causing resistance to taxane-type chemotherapy in triple negative breast cancer Scientific Reports TNBC Cancer Disparity AURKA AURKB Neoadjuvant Chemotherapy |
| title | Proteomic profiling identifies upregulation of aurora kinases causing resistance to taxane-type chemotherapy in triple negative breast cancer |
| title_full | Proteomic profiling identifies upregulation of aurora kinases causing resistance to taxane-type chemotherapy in triple negative breast cancer |
| title_fullStr | Proteomic profiling identifies upregulation of aurora kinases causing resistance to taxane-type chemotherapy in triple negative breast cancer |
| title_full_unstemmed | Proteomic profiling identifies upregulation of aurora kinases causing resistance to taxane-type chemotherapy in triple negative breast cancer |
| title_short | Proteomic profiling identifies upregulation of aurora kinases causing resistance to taxane-type chemotherapy in triple negative breast cancer |
| title_sort | proteomic profiling identifies upregulation of aurora kinases causing resistance to taxane type chemotherapy in triple negative breast cancer |
| topic | TNBC Cancer Disparity AURKA AURKB Neoadjuvant Chemotherapy |
| url | https://doi.org/10.1038/s41598-025-87315-x |
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