Publication
ATF3 reduces migration capacity by regulation of matrix metalloproteinases via NFB and STAT3 inhibition in glioblastoma
Journal Paper/Review - Feb 27, 2017
Guenzle Jessica, Wolf Louisa J, Garrelfs Nicklas W C, Goeldner Jonathan M, Osterberg Nadja, Schindler Cora R, Saavedra Joseph E, Weyerbrock Astrid
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Brief description/objective
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 cells. 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 NFB 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.