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

Silencing Aurora A leads to re-sensitization of breast cancer cells to Taxol through downregulation of SRC-mediated ERK and mTOR pathways. Oncol Rep. 2017 Aug 14;: Authors: Li Y, Zhou W, Tang K, Chen X, Feng Z, Chen J 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....
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research