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: 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
• Journal: Molecular cancer research : MCR (Mol Cancer Res) Vol. 10 Issue 1 Pg. 52-65 (Jan 2012) ISSN: 1557-3125 [Electronic] United States
• PMID: 22080479 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• RNA, Small Interfering
• Oxidoreductases
• STEAP1 protein, human

Topics

• Animals
• Antigens, Neoplasm (genetics, metabolism, physiology)
• Bone Neoplasms (genetics, metabolism, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic (drug effects)
• Gene Knockdown Techniques
• Humans
• Mice
• Mice, Inbred BALB C
• Mice, Transgenic
• Microarray Analysis
• Neoplasm Invasiveness
• Oxidative Stress (drug effects, genetics)
• Oxidoreductases (antagonists & inhibitors, genetics, metabolism, physiology)
• Phenotype
• Proteomics
• RNA, Small Interfering (pharmacology)
• Sarcoma, Ewing (genetics, metabolism, pathology)