TY - JOUR
T1 - Extracellular superoxide dismutase and its role in cancer
AU - Griess, Brandon
AU - Tom, Eric
AU - Domann, Frederick
AU - Teoh-Fitzgerald, Melissa
N1 - Funding Information:
This work was financially supported by grants from the NIH R01 CA115438 (FE Domann), NIH R0I-CA182086A (Teoh-Fitzgerald), Redox Biology Pilot Project Fund (NTSBRDF, Uni. of Nebraska, Lincoln) (Teoh-Fitzgerald), and Nebraska Department of Health and Human Services Award LB506 (Teoh-Fitzgerald). Brandon Griess was supported by the Eppley Institute in Cancer Biology Training Grant (NCI T32CA009476 ).
Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/11
Y1 - 2017/11
N2 - Reactive oxygen species (ROS) are increasingly recognized as critical determinants of cellular signaling and a strict balance of ROS levels must be maintained to ensure proper cellular function and survival. Notably, ROS is increased in cancer cells. The superoxide dismutase family plays an essential physiological role in mitigating deleterious effects of ROS. Due to the compartmentalization of ROS signaling, EcSOD, the only superoxide dismutase in the extracellular space, has unique characteristics and functions in cellular signal transduction. In comparison to the other two intracellular SODs, EcSOD is a relatively new comer in terms of its tumor suppressive role in cancer and the mechanisms involved are less well understood. Nevertheless, the degree of differential expression of this extracellular antioxidant in cancer versus normal cells/tissues is more pronounced and prevalent than the other SODs. A significant association of low EcSOD expression with reduced cancer patient survival further suggests that loss of extracellular redox regulation promotes a conducive microenvironment that favors cancer progression. The vast array of mechanisms reported in mediating deregulation of EcSOD expression, function, and cellular distribution also supports that loss of this extracellular antioxidant provides a selective advantage to cancer cells. Moreover, overexpression of EcSOD inhibits tumor growth and metastasis, indicating a role as a tumor suppressor. This review focuses on the current understanding of the mechanisms of deregulation and tumor suppressive function of EcSOD in cancer.
AB - Reactive oxygen species (ROS) are increasingly recognized as critical determinants of cellular signaling and a strict balance of ROS levels must be maintained to ensure proper cellular function and survival. Notably, ROS is increased in cancer cells. The superoxide dismutase family plays an essential physiological role in mitigating deleterious effects of ROS. Due to the compartmentalization of ROS signaling, EcSOD, the only superoxide dismutase in the extracellular space, has unique characteristics and functions in cellular signal transduction. In comparison to the other two intracellular SODs, EcSOD is a relatively new comer in terms of its tumor suppressive role in cancer and the mechanisms involved are less well understood. Nevertheless, the degree of differential expression of this extracellular antioxidant in cancer versus normal cells/tissues is more pronounced and prevalent than the other SODs. A significant association of low EcSOD expression with reduced cancer patient survival further suggests that loss of extracellular redox regulation promotes a conducive microenvironment that favors cancer progression. The vast array of mechanisms reported in mediating deregulation of EcSOD expression, function, and cellular distribution also supports that loss of this extracellular antioxidant provides a selective advantage to cancer cells. Moreover, overexpression of EcSOD inhibits tumor growth and metastasis, indicating a role as a tumor suppressor. This review focuses on the current understanding of the mechanisms of deregulation and tumor suppressive function of EcSOD in cancer.
KW - Cancer
KW - EcSOD
KW - Epigenetic
KW - Heparin binding domain
KW - Loss of heterozygosity
KW - Metastasis
KW - Oxidative tumor microenvironment
KW - Reactive oxygen species
KW - Recurrence
KW - Relapse free survival
KW - SOD3
KW - Single nucleotide polymorphism
KW - Tumor suppressor
KW - microRNA-21
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U2 - 10.1016/j.freeradbiomed.2017.08.013
DO - 10.1016/j.freeradbiomed.2017.08.013
M3 - Review article
C2 - 28842347
AN - SCOPUS:85028515541
VL - 112
SP - 464
EP - 479
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
SN - 0891-5849
ER -