Crystal structure of bacterial cell-surface alginate-binding protein with an M75 peptidase motif |
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Authors: | Maruyama Yukie Ochiai Akihito Mikami Bunzo Hashimoto Wataru Murata Kousaku |
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Institution: | Breast Disease Center, Southwest Hospital, Third Military Medical University, Gaotanyan Street 30, Chongqing 400038, PR China |
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Abstract: | Receptor activator of NF-κB (RANK) and RANK ligand (RANKL) are known to play an important role in the development and progression of breast cancer. However, the mechanisms by which stimuli regulate the expression of RANK and RANKL in breast cancer cells are largely unknown. In this study, we show that hypoxia, a common feature of malignant tumors, can enhance the expression of RANK and RANKL mRNA and protein in MDA-MB-231 and MCF-7 breast cancer cells. In addition, we found that hypoxia induced hypoxia-inducible factor-1 alpha (HIF-1α) and phosphorylation of Akt, resulting in upregulation of RANK and RANKL expression; HIF-1α-targeted siRNA and PI3K-Akt inhibitor abrogated this upregulation in MDA-MB-231 cells. Furthermore, we also observed that hypoxia accelerated RANKL-mediated cell migration, which was inhibited following HIF-1α knockdown and PI3K-Akt inhibition. Thus, we provide evidence that hypoxia upregulates RANK and RANKL expression and increases RANKL-induced cell migration via the PI3K/Akt-HIF-1α pathway. |
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Keywords: | Abbreviations: RANK receptor activator of NF-κB RANKL receptor activator of NF-κB ligand OPG osteoprotegerin PI3K the phosphoinositide 3-kinase HIF hypoxia-inducible factor |
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