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

  • Published online on: August 14, 2017     https://doi.org/10.3892/or.2017.5908
  • Pages: 2011-2022
  • Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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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October-2017
Volume 38 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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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