title: STEAP1 is associated with the invasive and oxidative stress phenotype of Ewing tumors.
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.
authors.affiliation: Children's Cancer Research and Roman Herzog Comprehensive Cancer Center, Laboratory of Functional Genomics and Transplantation Biology, Germany. thomas.gruenewald@lrz.tum.de
authors.forename: Thomas G P
authors.initials: TG
authors.lastname: Grunewald
authors.forename: Isabel
authors.initials: I
authors.lastname: Diebold
authors.forename: Irene
authors.initials: I
authors.lastname: Esposito
authors.forename: Stephanie
authors.initials: S
authors.lastname: Plehm
authors.forename: Kristina
authors.initials: K
authors.lastname: Hauer
authors.forename: Uwe
authors.initials: U
authors.lastname: Thiel
authors.forename: Patricia
authors.initials: P
authors.lastname: da Silva-Buttkus
authors.forename: Frauke
authors.initials: F
authors.lastname: Neff
authors.forename: Rebekka
authors.initials: R
authors.lastname: Unland
authors.forename: Carsten
authors.initials: C
authors.lastname: Müller-Tidow
authors.forename: Colette
authors.initials: C
authors.lastname: Zobywalski
authors.forename: Katharina
authors.initials: K
authors.lastname: Lohrig
authors.forename: Urs
authors.initials: U
authors.lastname: Lewandrowski
authors.forename: Albert
authors.initials: A
authors.lastname: Sickmann
authors.forename: Olivia
authors.initials: O
authors.lastname: Prazeres da Costa
authors.forename: Agnes
authors.initials: A
authors.lastname: Görlach
authors.forename: Andrea
authors.initials: A
authors.lastname: Cossarizza
authors.forename: Elke
authors.initials: E
authors.lastname: Butt
authors.forename: Günther H S
authors.initials: GH
authors.lastname: Richter
authors.forename: Stefan
authors.initials: S
authors.lastname: Burdach
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D046228:Microarray Analysis; D009361:Neoplasm Invasiveness; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010641:Phenotype; D040901:Proteomics; D034741:RNA, Small Interfering / Q000494:pharmacology; D012512:Sarcoma, Ewing / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D000951:Antigens, Neoplasm; D034741:RNA, Small Interfering; D010088:Oxidoreductases; C432763:STEAP1 protein, human