Open Access

Quantitative phosphoproteomics reveals genistein as a modulator of cell cycle and DNA damage response pathways in triple-negative breast cancer cells

  • Authors:
    • Yi Fang
    • Qian Zhang
    • Xin Wang
    • Xue Yang
    • Xiangyu Wang
    • Zhen Huang
    • Yuchen Jiao
    • Jing Wang
  • View Affiliations

  • Published online on: January 11, 2016     https://doi.org/10.3892/ijo.2016.3327
  • Pages: 1016-1028
  • Copyright: © Fang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Around one sixth of breast cancer cases are classified as triple-negative breast cancer (TNBC), named after the absence of the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2); however, patients with TNBC suffer from poor clinical outcome and shortage of targeted therapy. Genistein, an estrogenic soy isoflavone, shows anticancer effects in TNBC cells such as inducing G2/M cell cycle arrest and apoptosis. However, the underlying mechanism of its anticancer effects is poorly understood and its elucidation can help the development of novel therapeutic strategies for TNBC. In this study, by combining isobaric tag-based TMT labeling with titanium dioxide-based phosphopeptide enrichment, we quantitated 5,445 phosphorylation sites on 2,008 phosphoproteins in the TNBC cell line MDA-MB-231, upon genistein treatment. Our analysis revealed 332 genistein-regulated phosphorylation sites on 226 proteins. Our data show that genistein can regulate several biological processes during the cell cycle, including DNA replication, cohesin complex cleavage, and kinetochore formation. Furthermore, genistein can also activate DNA damage response, including activation of ATR and BRCA1 complex. Overall, our study presents evidence at a phosphoproteomic level that genistein is able to inhibit TNBC cell growth by regulating the cell cycle and DNA damage response in a more complex manner. Our findings help elucidate the mechanisms through which genistein exerts its anticancer effects in TNBC cells.
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March 2016
Volume 48 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Copy and paste a formatted citation
APA
Fang, Y., Zhang, Q., Wang, X., Yang, X., Wang, X., Huang, Z. ... Wang, J. (2016). Quantitative phosphoproteomics reveals genistein as a modulator of cell cycle and DNA damage response pathways in triple-negative breast cancer cells. International Journal of Oncology, 48, 1016-1028. https://doi.org/10.3892/ijo.2016.3327
MLA
Fang, Y., Zhang, Q., Wang, X., Yang, X., Wang, X., Huang, Z., Jiao, Y., Wang, J."Quantitative phosphoproteomics reveals genistein as a modulator of cell cycle and DNA damage response pathways in triple-negative breast cancer cells". International Journal of Oncology 48.3 (2016): 1016-1028.
Chicago
Fang, Y., Zhang, Q., Wang, X., Yang, X., Wang, X., Huang, Z., Jiao, Y., Wang, J."Quantitative phosphoproteomics reveals genistein as a modulator of cell cycle and DNA damage response pathways in triple-negative breast cancer cells". International Journal of Oncology 48, no. 3 (2016): 1016-1028. https://doi.org/10.3892/ijo.2016.3327