title: Overexpression of ErbB2 renders breast cancer cells susceptible to 3-BrPA through the increased dissociation of hexokinase II from mitochondrial outer membrane.
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 cytochromecinto 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 IIin vitroandin vivo.
authors.affiliation: Department of Anesthesiology, 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.
authors.forename: Sujie
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of General Surgery, China-Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China.
authors.forename: Xuebo
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of General Surgery, China-Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China.
authors.forename: Hongyong
authors.initials: H
authors.lastname: Jin
authors.affiliation: Department of General Surgery, China-Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China.
authors.forename: Shengnan
authors.initials: S
authors.lastname: Ren
authors.affiliation: Department of General Surgery, China-Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of General Surgery, China-Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China.
authors.forename: Xuedong
authors.initials: X
authors.lastname: Fang
authors.affiliation: Central Research Laboratory, The Second Hospital, Jilin University, Changchun, Jilin 130041, P.R. China.
authors.forename: Guizhen
authors.initials: G
authors.lastname: Zhang
keywords: 3-BrPA; ErbB2; hexokinase II