title: Manganese superoxide dismutase mediates anoikis resistance and tumor metastasis in nasopharyngeal carcinoma.
abstract: Metastatic cancer cells are able to survive the loss of attachment to the extracellular matrix (ECM) by developing resistance to anoikis, a specialized form of apoptosis. Here we investigated resistance to anoikis in nasopharyngeal carcinoma cells (NPC). When detached in culture, the highly metastatic S18 NPC cell line exhibited strong resistance to anoikis, as compared to the poorly metastatic S26 NPC cell line. With loss of attachment, S18 cells had lower levels of reactive oxygen species (ROS) and higher levels of manganese superoxide dismutase (MnSOD), an essential mitochondrial antioxidant enzyme. MnSOD knockdown increased the levels of ROS and diminished resistance to anoikis in S18 cells. Conversely, removal of reactive oxygen species (ROS) using NAC or overexpression of MnSOD in S26 cells induced resistance to anoikis. Blocking β-catenin through RNA interference down-regulated MnSOD expression and enhanced anoikis in S18 cells, while β-catenin overexpression enhanced MnSOD expression and suppressed anoikis in S26 cells. In addition, knockdown of MnSOD in S18 cells reduced colony formation in vitro and ameliorated lung metastasis in vivo. In patients with NPC, MnSOD expression was positively correlated with pathologic tumor stages and negatively correlated with overall survival. These results establish MnSOD as a key mediator of anoikis resistance and tumor metastasis and suggest that β-catenin/MnSOD could be a therapeutic target in NPC.
authors.affiliation: Program of Molecular Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.|Department of Biochemistry, Guangzhou Medical University, Guangzhou, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Li
authors.affiliation: Program of Molecular Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Yuling
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Program of Molecular Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Ti
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Program of Molecular Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Chuanghua
authors.initials: C
authors.lastname: Luo
authors.affiliation: Program of Molecular Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Jinye
authors.initials: J
authors.lastname: Xie
authors.affiliation: Program of Molecular Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Qi
authors.affiliation: Program of Molecular Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Zhonghan
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Physiology, University of Oklahoma, Health Sciences Center, Oklahoma City, USA.
authors.forename: JianXing
authors.initials: J
authors.lastname: Ma
authors.affiliation: Program of Molecular Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.|China Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Ministry of Education, Guangzhou, China.
authors.forename: Guoquan
authors.initials: G
authors.lastname: Gao
authors.affiliation: Program of Molecular Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.|Key Laboratory of Functional Molecules from Marine Microorganisms (Sun Yat-Sen University), Department of Education of Guangdong Province, Guangzhou, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Yang
mesh_terms: D000818:Animals; D023102:Anoikis; D002277:Carcinoma / Q000201:enzymology* / Q000235:genetics / Q000556:secondary; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000517:prevention & control / Q000556:secondary; D008297:Male; D008819:Mice, Nude; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism; D000099156:Superoxide Dismutase 2
chemical_list: D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D051176:beta Catenin; D000099156:Superoxide Dismutase 2; C495270:CTNNB1 protein, human
keywords: MnSOD; anoikis; nasopharyngeal carcinoma; reactive oxygen species; β-catenin