Manganese superoxide dismutase promotes anoikis resistance and tumor metastasis

doi:10.1038/cddis.2013.20

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	Manganese superoxide dismutase promotes anoikis resistance and tumor metastasis
	Kamarajugadda, S; Cai, Q; Chen, H; Nayak, S; Zhu, J; He, M; Jin, Y; Zhang, Y; Ai, L; Martin, SS
刊名	CELL DEATH & DISEASE
	2013-02
卷号	4 页码:-
关键词	anoikis ROS MnSOD NF kappa B metastasis NRF2
ISSN号	2041-4889
DOI	10.1038/cddis.2013.20
文献子类	Article
英文摘要	Normal cells require adhesion to extracellular matrix for survival. Cell detachment causes a drastic increase in reactive oxygen species (ROS) that promotes anoikis. In the present study, we observed that upon detachment from matrix, human mammary epithelial cells strongly upregulate manganese superoxide dismutase (MnSOD, or SOD2), a principal mitochondrial antioxidant enzyme that detoxifies ROS through dismutation of superoxide. Induction of MnSOD by cell detachment is dependent on the NF kappa B transcription factor. Detachment of mammary epithelial cells potently increases mitochondrial superoxide levels, which are further elevated by depletion of MnSOD in suspended cells. Consequently, cells depleted of MnSOD are hypersensitive to matrix detachment and exhibit increased anoikis. These results suggest that detachment-induced MnSOD counters mitochondrial superoxide accumulation and confers anoikis resistance. Taken together with our previous finding that detached cells evade excessive ROS production by attenuating oxidative metabolism of glucose, we conclude that mammary epithelial cells coordinate their responses to detachment through increasing MnSOD and decreasing ROS generation from mitochondrial glucose oxidation, thereby mitigating anoikis. Anoikis is a barrier to tumor metastasis. Indeed, MnSOD expression is elevated in human breast cancer metastases compared with primary tumors. Expression of MnSOD correlates with histologic tumor grades in human cancer and contributes to cancer cell's resistance to anoikis. Our study suggests that inhibition of ROS detoxification coupled with stimulation of glucose oxidative metabolism may be an efficient strategy to enhance anoikis and block metastasis. Cell Death and Disease (2013) 4, e504; doi:10.1038/cddis.2013.20; published online 21 February 2013
学科主题	Cell Biology
出版地	LONDON
项目编号	National Cancer Institute [R01CA137021] ; Florida Bankhead-Coley Cancer Research Program [09BN-12-23092, 2BT01]
语种	英语
WOS记录号	WOS:000315769500024
内容类型	期刊论文
源URL	[http://ir.lzu.edu.cn/handle/262010/125782]
专题	第一临床医学院_期刊论文
通讯作者	Kamarajugadda, S (reprint author), Univ Florida, Dept Biochem & Mol Biol, POB 100245, Gainesville, FL 32610 USA.
推荐引用方式 GB/T 7714	Kamarajugadda, S,Cai, Q,Chen, H,et al. Manganese superoxide dismutase promotes anoikis resistance and tumor metastasis[J]. CELL DEATH & DISEASE,2013,4:-.
APA	Kamarajugadda, S.,Cai, Q.,Chen, H.,Nayak, S.,Zhu, J.,...&Kamarajugadda, S .(2013).Manganese superoxide dismutase promotes anoikis resistance and tumor metastasis.CELL DEATH & DISEASE,4,-.
MLA	Kamarajugadda, S,et al."Manganese superoxide dismutase promotes anoikis resistance and tumor metastasis".CELL DEATH & DISEASE 4(2013):-.