title: 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.
authors: Department of Biosciences, University of Oslo, Oslo, Norway Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway.
authors: Yang
authors: Y
authors: Jin
authors: Department of Biosciences, University of Oslo, Oslo, Norway.
authors: Ling
authors: L
authors: Wang
authors: Department of Biosciences, University of Oslo, Oslo, Norway.
authors: Su
authors: S
authors: Qu
authors: Department of Biosciences, University of Oslo, Oslo, Norway Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway.
authors: Xia
authors: X
authors: Sheng
authors: Department of Tumor Biology, Oslo University Hospital, Oslo, Norway.
authors: Alexandr
authors: A
authors: Kristian
authors: Department of Tumor Biology, Oslo University Hospital, Oslo, Norway.
authors: Gunhild M
authors: GM
authors: Mælandsmo
authors: Department of Biosciences, University of Oslo, Oslo, Norway.
authors: Nora
authors: N
authors: Pällmann
authors: Department of Experimental Therapeutics, MD Anderson Cancer Center, Houston, TX, USA.
authors: Erkan
authors: E
authors: Yuca
authors: Department of Experimental Therapeutics, MD Anderson Cancer Center, Houston, TX, USA.
authors: Ibrahim
authors: I
authors: Tekedereli
authors: Department of Experimental Therapeutics, MD Anderson Cancer Center, Houston, TX, USA.
authors: Kivanc
authors: K
authors: Gorgulu
authors: Department of Experimental Therapeutics, MD Anderson Cancer Center, Houston, TX, USA.
authors: Neslihan
authors: N
authors: Alpay
authors: Gynecological Oncology, MD Anderson Cancer Center, Houston, TX, USA.
authors: Anil
authors: A
authors: Sood
authors: Department of Experimental Therapeutics, MD Anderson Cancer Center, Houston, TX, USA.
authors: Gabriel
authors: G
authors: Lopez-Berestein
authors: The Vancouver Prostate Centre, Vancouver, BC, Canada.
authors: Ladan
authors: L
authors: Fazli
authors: The Vancouver Prostate Centre, Vancouver, BC, Canada.
authors: Paul
authors: P
authors: Rennie
authors: Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway Division of Pathology, Oslo University Hospital, Oslo, Norway Division of Surgery, Oslo University Hospital, Oslo, Norway.
authors: Bjørn
authors: B
authors: Risberg
authors: Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway Division of Pathology, Oslo University Hospital, Oslo, Norway Division of Surgery, Oslo University Hospital, Oslo, Norway Center for Cancer Biomedicine, University of Oslo, Oslo, Norway.
authors: Håkon
authors: H
authors: Wæhre
authors: Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway Center for Cancer Biomedicine, University of Oslo, Oslo, Norway Department of Informatics, University of Oslo, Oslo, Norway.
authors: Håvard E
authors: HE
authors: Danielsen
authors: Department of Experimental Therapeutics, MD Anderson Cancer Center, Houston, TX, USA.
authors: Bulent
authors: B
authors: Ozpolat
authors: Department of Biosciences, University of Oslo, Oslo, Norway Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway fahris@ibv.uio.no.
authors: Fahri
authors: F
authors: Saatcioglu
mesh_terms: D051701:Activating Transcription Factor 4 / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D038181:FMN Reductase / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018384:Oxidative Stress; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D017382:Reactive Oxygen Species; D014183:Transplantation, Heterologous
chemical_list: C497109:ATF4 protein, human; D008565:Membrane Proteins; D017382:Reactive Oxygen Species; D051701:Activating Transcription Factor 4; D010088:Oxidoreductases; C503310:STEAP4 protein, human; D038181:FMN Reductase; C023903:ferric citrate iron reductase
keywords: activating transcription factor 4; iron reductase; prostate cancer; reactive oxygen species; six transmembrane protein of prostate 2