Overexpression of ErbB2 renders breast cancer cells susceptible to 3-BrPA through the increased dissociation of hexokinase II from mitochondrial outer membrane

  • Authors:
    • Sujie Gao
    • Xuebo Chen
    • Hongyong Jin
    • Shengnan Ren
    • Zhuo Liu
    • Xuedong Fang
    • Guizhen Zhang
  • View Affiliations

  • Published online on: December 21, 2015     https://doi.org/10.3892/ol.2015.4043
  • Pages: 1567-1573
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Abstract

ErbB2 is known to upregulate glycolysis in breast cancer, however, the precise mechanisms remain unclear. In the present study, ErbB2 upregulated Hexokinase II (HK II) activity by increasing the binding of HK II to the mitochondrial outer membrane. Dysregulated glucose metabolism in high ErbB2‑expressing breast cancer cells induces susceptibility to glucose starvation and glycolysis inhibition. Additionally, HK II has a tendency to dissociate from the mitochondria outer membrane in ErbB2‑overexpressing cells following treatment with the HK II inhibitor, 3‑BrPA. Furthermore, 3-BrPA treatment results in decreased mitochondria membrane potential and release of cytochrome c into cytoplasm in ErbB2-overexpressing cells, leading to activation of the mitochondrial apoptotic signaling pathway. In summary, the results demonstrate a novel mechanism for ErbB2-activated glycolysis and reveal that 3‑BrPA is effective in reducing ErbB2‑positive breast cancer cell viability by targeting HK II in vitro and in vivo.
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February-2016
Volume 11 Issue 2

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Gao S, Chen X, Jin H, Ren S, Liu Z, Fang X and Zhang G: Overexpression of ErbB2 renders breast cancer cells susceptible to 3-BrPA through the increased dissociation of hexokinase II from mitochondrial outer membrane. Oncol Lett 11: 1567-1573, 2016.
APA
Gao, S., Chen, X., Jin, H., Ren, S., Liu, Z., Fang, X., & Zhang, G. (2016). Overexpression of ErbB2 renders breast cancer cells susceptible to 3-BrPA through the increased dissociation of hexokinase II from mitochondrial outer membrane. Oncology Letters, 11, 1567-1573. https://doi.org/10.3892/ol.2015.4043
MLA
Gao, S., Chen, X., Jin, H., Ren, S., Liu, Z., Fang, X., Zhang, G."Overexpression of ErbB2 renders breast cancer cells susceptible to 3-BrPA through the increased dissociation of hexokinase II from mitochondrial outer membrane". Oncology Letters 11.2 (2016): 1567-1573.
Chicago
Gao, S., Chen, X., Jin, H., Ren, S., Liu, Z., Fang, X., Zhang, G."Overexpression of ErbB2 renders breast cancer cells susceptible to 3-BrPA through the increased dissociation of hexokinase II from mitochondrial outer membrane". Oncology Letters 11, no. 2 (2016): 1567-1573. https://doi.org/10.3892/ol.2015.4043