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dc.contributor.authorTochhawng, Lalchhandami
dc.contributor.authorDeng, Shuo
dc.contributor.authorGanesan, Pugalenthi
dc.contributor.authorKumar, Alan Prem
dc.contributor.authorLim, Kiat Hon
dc.contributor.authorYang, Henry
dc.contributor.authorHooi, Shing Chuan
dc.contributor.authorGoh, Yaw Chong
dc.contributor.authorMaciver, Sutherland K.
dc.contributor.authorPervaiz, Shazib
dc.contributor.authorYap, Celestial T.
dc.date.accessioned2016-12-21T13:50:18Z
dc.date.available2016-12-21T13:50:18Z
dc.date.issued2016-07-06
dc.identifier.citationTochhawng L, Deng S, Pugalenthi G, Kumar AP, Lim KH, et al. (2016) Gelsolin-Cu/ZnSOD interaction alters intracellular reactive oxygen species levels to promote cancer cell invasion. Oncotarget. Available: http://dx.doi.org/10.18632/oncotarget.10451.
dc.identifier.issn1949-2553
dc.identifier.pmid27391159
dc.identifier.doi10.18632/oncotarget.10451
dc.identifier.urihttp://hdl.handle.net/10754/622049
dc.description.abstractThe actin-binding protein, gelsolin, is a well known regulator of cancer cell invasion. However, the mechanisms by which gelsolin promotes invasion are not well established. As reactive oxygen species (ROS) have been shown to promote cancer cell invasion, we investigated on the hypothesis that gelsolin-induced changes in ROS levels may mediate the invasive capacity of colon cancer cells. Herein, we show that increased gelsolin enhances the invasive capacity of colon cancer cells, and this is mediated via gelsolin's effects in elevating intracellular superoxide (O2 .-) levels. We also provide evidence for a novel physical interaction between gelsolin and Cu/ZnSOD, that inhibits the enzymatic activity of Cu/ZnSOD, thereby resulting in a sustained elevation of intracellular O2 .-. Using microarray data of human colorectal cancer tissues from Gene Omnibus, we found that gelsolin gene expression positively correlates with urokinase plasminogen activator (uPA), an important matrix-degrading protease invovled in cancer invasion. Consistent with the in vivo evidence, we show that increased levels of O2 .- induced by gelsolin overexpression triggers the secretion of uPA. We further observed reduction in invasion and intracellular O2 .- levels in colon cancer cells, as a consequence of gelsolin knockdown using two different siRNAs. In these cells, concurrent repression of Cu/ ZnSOD restored intracellular O2 .- levels and rescued invasive capacity. Our study therefore identified gelsolin as a novel regulator of intracellular O2 .- in cancer cells via interacting with Cu/ZnSOD and inhibiting its enzymatic activity. Taken together, these findings provide insight into a novel function of gelsolin in promoting tumor invasion by directly impacting the cellular redox milieu.
dc.description.sponsorshipThe authors thank Dr. Thai Tran (National University of Singapore) and Ms Yongkang Qiao (National University of Singapore) for their help in calcium measurement.
dc.publisherImpact Journals, LLC
dc.relation.urlhttp://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=10451
dc.rightsAll site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/
dc.subjectAntioxidant
dc.subjectCu/ZnSOD
dc.subjectCytoskeleton
dc.subjectGelsolin
dc.subjectInvasion
dc.subjectROS
dc.titleGelsolin-Cu/ZnSOD interaction alters intracellular reactive oxygen species levels to promote cancer cell invasion
dc.typeArticle
dc.contributor.departmentBioinformatics
dc.contributor.departmentBioscience Core Lab
dc.identifier.journalOncotarget
dc.eprint.versionPublisher's Version/PDF
dc.contributor.institutionDepartment of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
dc.contributor.institutionDepartment of Biotechnology, School of Life Sciences, Assam Don Bosco University, Azara, Guwahati, India
dc.contributor.institutionDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
dc.contributor.institutionCancer Science Institute of Singapore, National University of Singapore, Singapore
dc.contributor.institutionNational University Cancer Institute, Singapore
dc.contributor.institutionCurtin Health Innovation Research Institute, Biosciences Research Precinct, School of Biomedical Sciences, Faculty of Health Sciences, Curtin UniversityWA, Australia
dc.contributor.institutionDepartment of Biological Sciences, University of North Texas, Denton, TX, United States
dc.contributor.institutionDepartment of Pathology, Singapore General Hospital, Singapore
dc.contributor.institutionDepartment of General Surgery, Singapore General Hospital, Singapore
dc.contributor.institutionDepartment of General Surgery, Mount Elizabeth Hospital, Singapore
dc.contributor.institutionCentre for Integrative Physiology, University of Edinburgh, United States
dc.contributor.institutionSchool of Biomedical Sciences, Faculty of Health Sciences, Curtin University, Perth, WA, Australia
dc.contributor.institutionNUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore
dc.contributor.institutionSingapore-MIT Alliance, Singapore
kaust.personGanesan, Pugalenthi
refterms.dateFOA2018-06-13T14:53:25Z
dc.date.published-online2016-07-06
dc.date.published-print2016-08-16


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