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RETRACTED ARTICLE: Aurora-A is a determinant of tamoxifen sensitivity through phosphorylation of ERα in breast cancer

Oncogene volume 33, pages 4985–4996 (2014)Cite this article

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This article was retracted on 23 February 2024

This article has been updated

Abstract

Despite the clinical success of tamoxifen, its resistance remains a major challenge in breast cancer. Here we show that Aurora-A determines tamoxifen sensitivity by regulation of oestrogen receptor (ER)α. Ectopic expression of Aurora-A decreases and depletion of Aurora-A enhances tamoxifen sensitivity in ERα-positive breast cancer. Elevated Aurora-A was significantly associated with the recurrence of ERα-positive tumours. Notably, Aurora-A inhibitor MLN8237, which is currently in clinical trial, synergizes with tamoxifen and overcomes tamoxifen resistance. Furthermore, Aurora-A interacts with and phosphorylates ERα on serine-167 and -305, leading to increase in ERα DNA-binding and transcriptional activity. Elevated levels of Aurora-A are significantly associated with disease-free survival in ERα-positive but not ERα-negative breast cancers. These data suggest that Aurora-A has a pivotal role in tamoxifen resistance and ERα is a bona fide substrate of Aurora-A. Thus, Aurora-A represents a prognostic marker in ERα-positive tumour and a critical therapeutic target in tamoxifen-resistant breast cancer, and Aurora-A inhibitor could be used as either an independent or concurrent agent in tamoxifen-resistant tumour.

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Acknowledgements

We appreciate Dr Kenji Fukasawa for his scientific input. We are grateful for Tissue Procurement, DNA Sequence, Proteomics and Image Core Facilities at H. Lee Moffitt Cancer Center for providing cancer specimens, sequencing and cell apoptosis analysis. This work was partially supported by grants from NIH grant CA160455 (JQC) and Florida James and Esther King Biomedical Research Program 1KG02 (JQC).

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Author notes

  1. X Q Zheng and J P Guo: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA

    X Q Zheng, J P Guo, H Yang, M Kanai, L L He, Y Y Li, J M Koomen & J Q Cheng

  2. Departments of Thyroid and Neck Tumour, Tianjin Medical University Cancer Institute and Hospital, Oncology Key Laboratory of cancer prevention and therapy, National Clinical Research Center of Cancer, Tianjin, PR China

    X Q Zheng & M Gao

  3. Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, Oncology Key Laboratory of cancer prevention and therapy, National Clinical Research Center of Cancer, Tianjin, PR China

    X Q Zheng & X B Ren

  4. Departments of Women’s Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA

    S Minton

  5. Departments of Women’s Pathology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA

    D Coppola

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  1. X Q Zheng
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Correspondence to J Q Cheng.

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Zheng, X., Guo, J., Yang, H. et al. RETRACTED ARTICLE: Aurora-A is a determinant of tamoxifen sensitivity through phosphorylation of ERα in breast cancer. Oncogene 33, 4985–4996 (2014). https://doi.org/10.1038/onc.2013.444

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  • DOI: https://doi.org/10.1038/onc.2013.444

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