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

Thomas G.P. Grunewald, Isabel Diebold, Irene Esposito, Stephanie Plehm, Kristina Hauer, Uwe Thiel, Patricia Da Silva-Buttkus, Frauke Neff, Rebekka Unland, Carsten Müller-Tidow, Colette Zobywalski, Katharina Lohrig, Urs Lewandrowski, Albert Sickmann, Olivia Prazeres Da Costa, Agnes Görlach, Andrea Cossarizza, Elke Butt, Günther H.S. Richter, Stefan Burdach

Research output: Contribution to journalArticlepeer-review

106 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)52-65
Number of pages14
JournalMolecular Cancer Research
Volume10
Issue number1
DOIs
StatePublished - Jan 2012

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