title: ATF3 reduces migration capacity by regulation of matrix metalloproteinases via NFκB and STAT3 inhibition in glioblastoma.
abstract: Glioblastoma is associated with poor survival and a high recurrence rate in patients due to inevitable uncontrolled infiltrative tumor growth. The elucidation of the molecular mechanisms may offer opportunities to prevent relapses. In this study we investigated the role of the activating transcription factor 3 (ATF3) in migration of GBM cellsin vitro. RNA microarray revealed that gene expression of ATF3 is induced by a variety of chemotherapeutics and experimental agents such as the nitric oxide donor JS-K (O2-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate). We found NFκB and STAT3 to be downstream targets inhibited by overexpression of ATF3. We demonstrate that ATF3 is directly involved in the regulation of matrix metalloproteinase expression and activation. Overexpression of ATF3 therefore leads to a significantly reduced migration capacity and induction of tissue inhibitors of matrix metalloproteinases. Our study for the first time identifies ATF3 as a potential novel therapeutic target in glioblastoma.
authors.affiliation: Department of Neurosurgery, Medical Center-University of Freiburg, Faculty of Medicine, Breisacher Strasse 64, Freiburg D-79106, Germany; University of Freiburg, Faculty of Biology, Schaenzlestrasse 1, Freiburg D-79104, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Guenzle
authors.affiliation: Department of Neurosurgery, Medical Center-University of Freiburg, Faculty of Medicine , Breisacher Strasse 64, Freiburg D-79106, Germany.
authors.forename: Louisa J
authors.initials: LJ
authors.lastname: Wolf
authors.affiliation: Department of Neurosurgery, Medical Center-University of Freiburg, Faculty of Medicine , Breisacher Strasse 64, Freiburg D-79106, Germany.
authors.forename: Nicklas W C
authors.initials: NW
authors.lastname: Garrelfs
authors.affiliation: Department of Neurosurgery, Medical Center-University of Freiburg, Faculty of Medicine , Breisacher Strasse 64, Freiburg D-79106, Germany.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Goeldner
authors.affiliation: Department of Neurosurgery, Medical Center-University of Freiburg, Faculty of Medicine , Breisacher Strasse 64, Freiburg D-79106, Germany.
authors.forename: Nadja
authors.initials: N
authors.lastname: Osterberg
authors.affiliation: Department of Neurosurgery, Medical Center-University of Freiburg, Faculty of Medicine , Breisacher Strasse 64, Freiburg D-79106, Germany.
authors.forename: Cora R
authors.initials: CR
authors.lastname: Schindler
authors.affiliation: Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute (NCI) at Frederick , Frederick, MD 21702, USA.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Saavedra
authors.affiliation: Department of Neurosurgery, Medical Center-University of Freiburg, Faculty of Medicine , Breisacher Strasse 64, Freiburg D-79106, Germany.
authors.forename: Astrid
authors.identifier: 0000-0001-9060-4462
authors.initials: A
authors.lastname: Weyerbrock