Loss of COX5B inhibits proliferation and promotes senescence via mitochondrial dysfunction in breast cancer
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Shui-Ping Gao1,2,*, He-Fen Sun1,2,*, Hong-Lin Jiang1,2, Liang-Dong Li1,2, Xin Hu1, Xiao-En Xu1,2 and Wei Jin1,2
1 Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, Shanghai, China
2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
* These authors have contributed equally to this work
Wei Jin, email:
Keywords: COX5B, proliferation, mitochondrial dysfunction, senescence, cytokine
Received: June 08, 2015 Accepted: October 14, 2015 Published: October 25, 2015
COX5B, a peripheral subunit of the cytochrome c oxidase complex, has previously been reported to maintain the stability of this complex. However, its functions and mechanisms involved in breast cancer progression remain unclear. Here, by performing SILAC assays in breast cancer cell models and detecting COX5B expression in tissues, we found that COX5B expression was elevated in breast cancer. Down-regulation of COX5B in breast cancer cell lines can suppress cell proliferation and induced cell senescence which was accompanied by elevating production of IL-8 and other cytokines. Interestingly, conditioned medium from COX5B knockdown cells could promote breast cancer cell migration. Mechanistic studies reveal that COX5B silence induces an increase in production of ROS, depolarization of MMP and a decrease in ATP. What’s more, silence of COX5B leads to metabolic disorders, such as increased glucose uptake and decreased lactate secretion. Collectively, our study shows that loss of COX5B induces mitochondrial dysfunction and subsequently leads to cell growth suppression and cell senescence. Cytokines such as IL-8 secreted by senescent cells may in turn alter the microenvironment which could enhance cell migration. These findings may provide a novel paradigm for the treatment which combined anti-cancer drugs with particular cytokine inhibitors such as IL-8 blockers.
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