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

Gao,Sujie; Chen,Xuebo; Jin,Hongyong; Ren,Shengnan; Liu,Zhuo; Fang,Xuedong; Zhang,Guizhen

doi:10.3892/ol.2015.4043

February-2016 Volume 11 Issue 2

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February-2016 Volume 11 Issue 2

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Article

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 / Copyright

Affiliations: Department of Anesthesiology, China-Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China, Department of General Surgery, China-Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China, Central Research Laboratory, The Second Hospital, Jilin University, Changchun, Jilin 130041, P.R. China
Pages: 1567-1573
|
Published online on: December 21, 2015

https://doi.org/10.3892/ol.2015.4043
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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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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

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

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