title: OTUB1 de-ubiquitinating enzyme promotes prostate cancer cell invasion in vitro and tumorigenesis in vivo.
abstract: BACKGROUND
  Ubiquitination is a highly dynamic and reversible process with a central role in cell homeostasis. Deregulation of several deubiquitinating enzymes has been linked to tumor development but their specific role in prostate cancer progression remains unexplored.
  
  
  METHODS
  RNAi screening was used to investigate the role of the ovarian tumor proteases (OTU) family of deubiquitinating enzymes on the proliferation and invasion capacity of prostate cancer cells. RhoA activity was measured in relation with OTUB1 effects on prostate cancer cell invasion. Tumor xenograft mouse model with stable OTUB1 knockdown was used to investigate OTUB1 influence in tumor growth.
  
  
  RESULTS
  Our RNAi screening identified OTUB1 as an important regulator of prostate cancer cell invasion through the modulation of RhoA activation. The effect of OTUB1 on RhoA activation is important for androgen-induced repression of p53 expression in prostate cancer cells. In localized prostate cancer tumors OTUB1 was found overexpressed as compared to normal prostatic epithelial cells. Prostate cancer xenografts expressing reduced levels of OTUB1 exhibit reduced tumor growth and reduced metastatic dissemination in vivo.
  
  
  CONCLUSIONS
  OTUB1 mediates prostate cancer cell invasion through RhoA activation and promotes tumorigenesis in vivo. Our results suggest that drugs targeting the catalytic activity of OTUB1 could potentially be used as therapeutics for metastatic prostate cancer.
authors.affiliation: The Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, 2200, Copenhagen, Denmark. diego.iglesias@cpr.ku.dk.
authors.forename: Diego
authors.initials: D
authors.lastname: Iglesias-Gato
authors.affiliation: The Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, 2200, Copenhagen, Denmark. yinchoy.chuan@gmail.com.
authors.forename: Yin-Choy
authors.initials: YC
authors.lastname: Chuan
authors.affiliation: The Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, 2200, Copenhagen, Denmark. jiangning@bjmu.edu.cn.|Tianjin Institute of Urology, Tianjin Medical University, 300211, Tianjin, China. jiangning@bjmu.edu.cn.
authors.forename: Ning
authors.initials: N
authors.lastname: Jiang
authors.affiliation: The Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, 2200, Copenhagen, Denmark. charlotte.svensson@cpr.ku.dk.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Svensson
authors.affiliation: The Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, 2200, Copenhagen, Denmark. jingbao06@gmail.com.|Tianjin Institute of Urology, Tianjin Medical University, 300211, Tianjin, China. jingbao06@gmail.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Bao
authors.affiliation: The Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, 2200, Copenhagen, Denmark. indranil.paul@cpr.ku.dk.
authors.forename: Indranil
authors.initials: I
authors.lastname: Paul
authors.affiliation: Section of Urology, Department of Surgical Science Karolinska Institutet, 17176, Stockholm, Sweden. lars.egevad@ki.se.
authors.forename: Lars
authors.initials: L
authors.lastname: Egevad
authors.affiliation: Target Discovery Institute, Nuffield Department of Clinical Medicine, University of Oxford, OX3 7BN, Oxford, UK. benedikt.kessler@ndm.ox.ac.uk.
authors.forename: Benedikt M
authors.initials: BM
authors.lastname: Kessler
authors.affiliation: Department of Medical Biosciences, Pathology, Umeå University, 90185, Umeå, Sweden. pernilla.wikstrom@medbio.umu.se.
authors.forename: Pernilla
authors.initials: P
authors.lastname: Wikström
authors.affiliation: Tianjin Institute of Urology, Tianjin Medical University, 300211, Tianjin, China. niuyuanjie9317@163.com.
authors.forename: Yuanjie
authors.initials: Y
authors.lastname: Niu
authors.affiliation: The Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, 2200, Copenhagen, Denmark. amilcar.flores@cpr.ku.dk.
authors.forename: Amilcar
authors.initials: A
authors.lastname: Flores-Morales
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D054875:Ubiquitination / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D016159:Tumor Suppressor Protein p53; D003546:Cysteine Endopeptidases; D020742:rhoA GTP-Binding Protein