title: Manganese superoxide dismutase promotes interaction of actin, S100A4 and Talin, and enhances rat gastric tumor cell invasion.
abstract: It has been demonstrated that cancer cells are under high levels of oxidative stress and express high levels of Manganese superoxide dismutase (MnSOD) to protect themselves and support the anabolic metabolism needed for growth and cell motility. The aim of this study was to identify proteins that may have a correlation with invasion and redox regulation by mitochondrial reactive oxygen species (ROS). MnSOD scavenges superoxide anions generated from mitochondria and is an important regulator of cellular redox status. Oxidative posttranslational modification of cysteine residues is a key mechanism that regulates protein structure and function. We hypothesized that MnSOD regulates intracellular reduced thiol status and promotes cancer invasion. A proteomic thiol-labeling approach with 5-iodoacetamidofluorescein was used to identify changes in intracellular reduced thiol-containing proteins. Our results demonstrate that overexpression of MnSOD maintained the major structural protein, actin, in a reduced state, and enhanced the invasion ability in gastric mucosal cancer cells, RGK1. We also found that the expression of Talin and S100A4 were increased in MnSOD-overexpressed RGK1 cells. Moreover, Talin bound not only with actin but also with S100A4, suggesting that the interaction of these proteins may, in part, contribute to the invasive ability of rat gastric cancer.
authors.affiliation: Department of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan ; Graduate Center for Toxicology, University of Kentucky, BBSRB Building 741 S. Limestone, B278 and 306 Health Sciences Research Building, 1095 V.A. Drive, Lexington, KY 40536, USA.
authors.forename: Hiroko P
authors.initials: HP
authors.lastname: Indo
authors.affiliation: Division of Gastroenterology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Ten-noudai, Tsukuba, Ibaraki 305-8577, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Matsui
authors.affiliation: Department of Molecular & Cellular Biochemistry and Center for Structural Biology, University of Kentucky, BBSRB Building 741 S. Limestone, B278 and 306 Health Sciences Research Building, 1095 V.A. Drive, Lexington, KY 40536, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Molecular & Cellular Biochemistry and Center for Structural Biology, University of Kentucky, BBSRB Building 741 S. Limestone, B278 and 306 Health Sciences Research Building, 1095 V.A. Drive, Lexington, KY 40536, USA.
authors.forename: Haining
authors.initials: H
authors.lastname: Zhu
authors.affiliation: The Heart Research Institute, 7 Eliza Street, Newtown, Sydney, NSW 2042, Australia ; Faculty of Medicine, Sydney Medical School, The University of Sydney, Edward Ford Building A27, Sydney, NSW 2006, Australia.
authors.forename: Clare L
authors.initials: CL
authors.lastname: Hawkins
authors.affiliation: The Heart Research Institute, 7 Eliza Street, Newtown, Sydney, NSW 2042, Australia ; Faculty of Medicine, Sydney Medical School, The University of Sydney, Edward Ford Building A27, Sydney, NSW 2006, Australia.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Davies
authors.affiliation: Graduate Center for Toxicology, University of Kentucky, BBSRB Building 741 S. Limestone, B278 and 306 Health Sciences Research Building, 1095 V.A. Drive, Lexington, KY 40536, USA.
authors.forename: Chontida
authors.initials: C
authors.lastname: Yarana
authors.affiliation: Graduate Center for Toxicology, University of Kentucky, BBSRB Building 741 S. Limestone, B278 and 306 Health Sciences Research Building, 1095 V.A. Drive, Lexington, KY 40536, USA.
authors.forename: Daret K
authors.initials: DK
authors.lastname: St Clair
authors.affiliation: Department of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan ; Department of Space Environmental Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
authors.forename: Hideyuki J
authors.initials: HJ
authors.lastname: Majima
keywords: MnSOD; ROS; actin binding protein; cancer invasion; reduced form of actin