分类： 生物学 >> 生物物理学 >> 肿瘤学 提交时间： 2016-05-15
Zhang, Bo
Wei, Peng
Hao, Junfeng
Zhao, Lijing
Zhang, Fenglin
Wei, Taotao
Wang, Jing
Huang, Zhen
Wei, Peng
Liu, Ying
Tu, Yaping
摘要： Tumor necrosis factor receptor-associated protein 1 (TRAP1) is abnormally expressed in many cancers. In this study, we showed that TRAP1 is aberrantly upregulated in breast tumors compared to control tissues. TRAP1 knockdown downregulates mitochondrial aerobic respiratory, sensitizes cells to lethal stimuli, and inhibited tumor growth in MDA-MB-231 and MCF-7 breast cancer cells in vivo. TRAP1 overexpression, however, enhances the capacity to cope with stress conditions. These evidences suggested that TRAP1 is required for tumorigenesis. We also found that TRAP1 regulates the mitochondrial morphology. Relatively lower TRAP1 levels are associated with the rod-shaped mitochondrial phenotype in invasive and metastatic MDA-MB-231 breast cancer cells; on the contrary, higher TRAP1 levels are associated with the tubular network-shaped mitochondrial phenotype in non-invasive MCF-7 cells. Interestingly, the expression of TRAP1 in human breast cancer specimens inversely correlates with tumor grade. Overexpression of TRAP1 in MDA-MB-231 cells causes mitochondrial fusion, triggers mitochondria to form tubular networks, and suppresses cell migration and invasion in vitro and in vivo. These data link TRAP1-regulated mitochondrial dynamics and function with tumorigenesis of breast cancer and suggested that TRAP1 may therefore be a potential target for breast cancer drug development.
分类： 生物学 >> 生物物理学 >> 生物物理、生物化学与分子生物学 提交时间： 2016-05-12
摘要： The insulin-mimetic and anti-diabetic properties of vanadium and related compounds have been well documented both in vitro and in vivo. However, the molecular basis of the link between vanadium and the insulin signaling pathway in diabetes mellitus is not fully described. We investigated the effects of reactive oxygen species (ROS) induced by oxidovanadium(IV) sulfate (VOSO4) on glucose uptake and the insulin signaling pathway in human hepatoma cell line HepG2. Exposure of cells to VOSO4 (5-50 mu M) resulted in an increase in glucose uptake, insulin receptor (IR) and protein kinase B (Akt) phosphorylation and intracellular ROS generation. Using Western blot, we found that catalase and sodium formate, but not superoxide dismutase, prevented the increase of hydroxyl radical (center dot OH) generation and significantly decreased VOSO4-induced IR and Akt phosphorylation. These results suggest that VOSO4-induced center dot OH radical, which is a signaling species, promotes glucose uptake via the IR/Akt signaling pathway. (C) 2015 Elsevier Inc. All rights reserved.
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