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Grunewald, T.G.* ; Diebold, I.* ; Esposito, I. ; Plehm, S.* ; Hauer, K.* ; Thiel, U.* ; Da Silva-Buttkus, P. ; Neff, F. ; Unland, R.* ; Müller-Tidow, C.* ; Zobywalski, C.* ; Lohrig, K.* ; Lewandrowski, U.* ; Sickmann, A.* ; da Costa, O.P.* ; Görlach, A.* ; Cossarizza, A.* ; Butt, E.* ; Richter, G.H.* ; Burdach, S.*

STEAP1 is associated with the invasive and oxidative stress phenotype of Ewing tumors.

Mol. Cancer Res. 10, 52-65 (2012)
DOI
Open Access Green as soon as Postprint is submitted to ZB.
Ewing tumors comprise the second most common type of bone-associated cancer in children and are characterized by oncogenic EWS/FLI1 fusion proteins and early metastasis. Compelling evidence suggests that elevated levels of intracellular oxidative stress contribute to enhanced aggressiveness of numerous cancers, possibly including Ewing tumors. Using comprehensive microarray analyses and RNA interference, we identified the six-transmembrane epithelial antigen of the prostate 1 (STEAP1)-a membrane-bound mesenchymal stem cell marker of unknown function-as a highly expressed protein in Ewing tumors compared with benign tissues and show its regulation by EWS/FLI1. In addition, we show that STEAP1 knockdown reduces Ewing tumor proliferation, anchorage-independent colony formation as well as invasion in vitro and decreases growth and metastasis of Ewing tumor xenografts in vivo. Moreover, transcriptome and proteome analyses as well as functional studies revealed that STEAP1 expression correlates with oxidative stress responses and elevated levels of reactive oxygen species that in turn are able to regulate redox-sensitive and proinvasive genes. In synopsis, our data suggest that STEAP1 is associated with the invasive behavior and oxidative stress phenotype of Ewing tumors and point to a hitherto unanticipated oncogenic function of STEAP1.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords 6-transmembrane epithelial antigen; Influences zyxin loccalization; Reactive oxygen; Endoplasmic; C-reticulum; Hydrogen-peroxide; Familiy tumors; Cancer Cells; Expression; Profileration; Prostate
ISSN (print) / ISBN 1541-7786
e-ISSN 1557-3125
Journal Molecular Cancer Research
Quellenangaben Volume: 10, Issue: 1, Pages: 52-65 Article Number: , Supplement: ,
Publisher American Association for Cancer Research (AACR)
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Pathology (PATH)