STAMP2 increases oxidative stress and is critical for prostate cancer

Abstract

The six transmembrane protein of prostate 2 (STAMP2) is an androgen-regulated gene whose mRNA expression is increased in prostate cancer (PCa). Here, we show that STAMP2 protein expression is increased in human PCa compared with benign prostate that is also correlated with tumor grade and treatment response. We also show that STAMP2 significantly increased reactive oxygen species (ROS) in PCa cells through its iron reductase activity which also depleted NADPH levels. Knockdown of STAMP2 expression in PCa cells inhibited proliferation, colony formation, and anchorage-independent growth, and significantly increased apoptosis. Furthermore, STAMP2 effects were, at least in part, mediated by activating transcription factor 4 (ATF4), whose expression is regulated by ROS. Consistent with in vitro findings, silencing STAMP2 significantly inhibited PCa xenograft growth in mice. Finally, therapeutic silencing of STAMP2 by systemically administered nanoliposomal siRNA profoundly inhibited tumor growth in two established preclinical PCa models in mice. These data suggest that STAMP2 is required for PCa progression and thus may serve as a novel therapeutic target.

Quantitative proteomics identifies STEAP4 as a critical regulator of mitochondrial dysfunction linking inflammation and colon cancer

“…All four STEAP proteins are increased in prostate cancer and play important role in prostate cancer development and progression (30)(31)(32)(33)(34). STEAP4 increases ROS in prostate cancer cells through its iron reductase activity (15). This supports our hypothesis that STEAP4 provides ferrous iron to mitochondria for maintaining normal respiratory function and producing free radicals (35).…”

Dietary supplementation with l-glutamate and l-aspartate alleviates oxidative stress in weaned piglets challenged with hydrogen peroxide

“…Oxidative stress generally results from an imbalance between pro-oxidative and anti-oxidative systems (El Assar et al 2013). Many investigations have revealed that oxidative stress is closely associated with the pathogenesis of many diseases such as intestinal inflammatory bowel (Mandalari et al 2011), diabetes (Togliatto et al 2015), and even cancers (Jin et al 2015). H 2 O 2 , a major ROS, is widely used as an oxidative stress stimulus.…”

Determination of Six Transmembrane Protein of Prostate 2 Gene Expression and Intracellular Localization in Prostate Cancer

“…Bu sebeple prostat kanseri hücrelerinde AR'yi hedef alan genler ve bunların yolakları tedavide önemli hedefler olabilir. Androjenle regüle olan ve prostat kanserinin patogenezinde önemli bir rol aldığı son çalışmalarda gösterilen genlerden biri six transmembrane protein of prostate (STAMP) ya da six transmembrane epithelial antigen of prostate (STEAP) gen ailesine üye olan STAMP2'dir (5,6,7). STAMP2'nin prostat kanserinde benign prostat dokusu ile karşılaştırıldığında aşırı derecede eksprese olduğu ve oksidatif stresi artırarak prostat kanseri patogenezinde rol alabileceği gösterilmiştir (5,6).…”

“…Androjenle regüle olan ve prostat kanserinin patogenezinde önemli bir rol aldığı son çalışmalarda gösterilen genlerden biri six transmembrane protein of prostate (STAMP) ya da six transmembrane epithelial antigen of prostate (STEAP) gen ailesine üye olan STAMP2'dir (5,6,7). STAMP2'nin prostat kanserinde benign prostat dokusu ile karşılaştırıldığında aşırı derecede eksprese olduğu ve oksidatif stresi artırarak prostat kanseri patogenezinde rol alabileceği gösterilmiştir (5,6). Bu çalışmada, STAMP2 geninin AR içeren [prostat kanserinin lenf nodu (LNCaP) hücre kültürleri, AR taşıyan] hücre kültürlerindeki ekspresyon profilinin androjenle regülasyonunu, RNA ve protein düzeyinde göstermek ve endojen STAMP2 proteininin hücre içi lokalizasyonunu belirlemek amaçlanmıştır.…”