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RETRACTED ARTICLE: Suppression of the xCT–CD44v antiporter system sensitizes triple-negative breast cancer cells to doxorubicin

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This article was retracted on 01 May 2015

Abstract

The xCT antiporter is known to be upregulated in 30 % of triple-negative breast cancer (TNBC) cell lines. The xCT–CD44 variant (CD44v) system regulates the levels of reactive oxygen species (ROS) in cancer cells and promotes tumor growth. Here, the role of this antiporter system in relation to chemotherapy was evaluated. MDA-MB-231 and MDA-MB-436 cells were transfected with lentiviral vectors expressing short hairpin RNA against xCT or CD44v. Following doxorubicin treatment, cellular proliferation was monitored, ROS were measured, and intracellular levels of cysteine and glutathione (GSH) were determined using liquid chromatography–mass spectrometry. A TNBC orthotopic tumor model was used to evaluate the impact of xCT–CD44v inhibition on doxorubicin efficacy in vivo. Doxorubicin treatment of TNBC cells caused increased expression of xCT through upregulation of CD44v. Consequently, the intracellular uptake of cystine increased, enabling rapid synthesis of GSH, and neutralization of doxorubicin-induced ROS. Suppression of xCT or CD44v impaired the defense against drug-induced oxidative stress, thereby sensitizing cells to doxorubicin. The importance of the xCT–CD44v in supporting tumor growth during doxorubicin treatment was also demonstrated in an in vivo tumor model of TNBC. These findings suggest that the antiporter system could serve as a target for increasing the anticancer efficacy of conventional therapy in patients with TNBC.

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Acknowledgments

We thank Prof. Osamu Nagano for providing the CD44v antibody. The research was supported by funds from Excellent Academic Backbone Program of Tenth People’s Hospital of Shanghai (No. 12XSGG102).

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Gastroenterology, The Tenth People’s Hospital of Shanghai, Tongji University, Shanghai, 200072, People’s Republic of China

    Feng Wang

  2. Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX, 77030, USA

    Yong Yang

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  2. Yong Yang
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Correspondence to Yong Yang.

Additional information

This article has been retracted at the request of the corresponding author due to submission of his article for publication without internal review and approval from his institution (Houston Methodist Research Institute).

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Wang, F., Yang, Y. RETRACTED ARTICLE: Suppression of the xCT–CD44v antiporter system sensitizes triple-negative breast cancer cells to doxorubicin. Breast Cancer Res Treat 147, 203–210 (2014). https://doi.org/10.1007/s10549-014-3068-6

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  • DOI: https://doi.org/10.1007/s10549-014-3068-6

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