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Article Open Access

Silencing Aurora A leads to re-sensitization of breast cancer cells to Taxol through downregulation of SRC-mediated ERK and mTOR pathways

  • Authors:
    • Yan Li
    • Wanqi Zhou
    • Ke Tang
    • Xiaoguang Chen
    • Zhiqiang Feng
    • Jindong Chen
  • View Affiliations / Copyright

    Affiliations: State Key Laboratory of Bioactive Substances and Functions of Nature Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, P.R. China, Beijing Key Laboratory of Active Substance Discovery and Drugability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, P.R. China, Department of Urology, University of Rochester Medical Center, Rochester, NY 14642, USA
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2011-2022
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    Published online on: August 14, 2017
       https://doi.org/10.3892/or.2017.5908
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Abstract

While Taxol has been reported to improve the clinical survival of breast cancer patients, subsequently developed drug-resistance of the cancer cells limits its final efficacy and applications. Previous studies suggested that Aurora A is involved in the development of the Taxol-resistance of breast cancer. We established Taxol-resistant breast cancer MCF-7/T cells and xenograft models to explore the role of Aurora A in Taxol resistant ER-positive breast cancer. Compared with their parental MCF-7/C cells, the Taxol-resistant MCF-7/T cells exhibited enhanced colony formation, less cell death and higher invasive ability. The resistant cells presented overexpressed Aurora A, elevated phosphorylated SRC and upregulated Ras/Raf/ERK and Akt/mTOR pathways. Silencing of Aurora A reduced the activity of SRC and downregulated the ERK and Akt/mTOR pathways, which led to re-sensitization of the resistant MCF-7/T cells to Taxol in vitro. These results suggested that the activation of Aurora A and the subsequent upregulation of ERK and Akt through SRC induced Taxol-resistance in breast cancer cells, and inhibiting Aurora A and the related SRC/EKT/Akt pathway could restore the sensitivity of breast cancer cells to Taxol. These results might shed light on the development of strategies to circumvent Taxol-related chemoresistance in breast cancer clinical practice.
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Copy and paste a formatted citation
Spandidos Publications style
Li Y, Zhou W, Tang K, Chen X, Feng Z and Chen J: Silencing Aurora A leads to re-sensitization of breast cancer cells to Taxol through downregulation of SRC-mediated ERK and mTOR pathways. Oncol Rep 38: 2011-2022, 2017.
APA
Li, Y., Zhou, W., Tang, K., Chen, X., Feng, Z., & Chen, J. (2017). Silencing Aurora A leads to re-sensitization of breast cancer cells to Taxol through downregulation of SRC-mediated ERK and mTOR pathways. Oncology Reports, 38, 2011-2022. https://doi.org/10.3892/or.2017.5908
MLA
Li, Y., Zhou, W., Tang, K., Chen, X., Feng, Z., Chen, J."Silencing Aurora A leads to re-sensitization of breast cancer cells to Taxol through downregulation of SRC-mediated ERK and mTOR pathways". Oncology Reports 38.4 (2017): 2011-2022.
Chicago
Li, Y., Zhou, W., Tang, K., Chen, X., Feng, Z., Chen, J."Silencing Aurora A leads to re-sensitization of breast cancer cells to Taxol through downregulation of SRC-mediated ERK and mTOR pathways". Oncology Reports 38, no. 4 (2017): 2011-2022. https://doi.org/10.3892/or.2017.5908
Copy and paste a formatted citation
x
Spandidos Publications style
Li Y, Zhou W, Tang K, Chen X, Feng Z and Chen J: Silencing Aurora A leads to re-sensitization of breast cancer cells to Taxol through downregulation of SRC-mediated ERK and mTOR pathways. Oncol Rep 38: 2011-2022, 2017.
APA
Li, Y., Zhou, W., Tang, K., Chen, X., Feng, Z., & Chen, J. (2017). Silencing Aurora A leads to re-sensitization of breast cancer cells to Taxol through downregulation of SRC-mediated ERK and mTOR pathways. Oncology Reports, 38, 2011-2022. https://doi.org/10.3892/or.2017.5908
MLA
Li, Y., Zhou, W., Tang, K., Chen, X., Feng, Z., Chen, J."Silencing Aurora A leads to re-sensitization of breast cancer cells to Taxol through downregulation of SRC-mediated ERK and mTOR pathways". Oncology Reports 38.4 (2017): 2011-2022.
Chicago
Li, Y., Zhou, W., Tang, K., Chen, X., Feng, Z., Chen, J."Silencing Aurora A leads to re-sensitization of breast cancer cells to Taxol through downregulation of SRC-mediated ERK and mTOR pathways". Oncology Reports 38, no. 4 (2017): 2011-2022. https://doi.org/10.3892/or.2017.5908
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