4.5 Article

STEAP1 Is Associated with the Invasive and Oxidative Stress Phenotype of Ewing Tumors

Journal

MOLECULAR CANCER RESEARCH
Volume 10, Issue 1, Pages 52-65

Publisher

AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1541-7786.MCR-11-0524

Keywords

-

Funding

  1. TU Munchen [B08-05, A09-02]
  2. Deutsche Forschungsgemeinschaft [GR3728/1.1, SFB/TR22, EB740/6.1]
  3. Wilhelm-Sander-Stiftung [2009.901.1]
  4. Ministerium fur Innovation
  5. Wissenschaft und Technologie des Landes Nordrhein-Westfalen
  6. EU
  7. Bundes-ministerium fur Bildung und Forschung (BMBF) [FK 01GM0870]
  8. Translational-Sarcoma-Research-Network

Ask authors/readers for more resources

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. Mol Cancer Res; 10(1); 52-65. (C) 2011 AACR.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.5
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available