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In this study, we show that two of the most frequently altered signaling pathways in prostate cancer, the androgen receptor and the phosphoinositide 3-kinase\/protein kinase B\/mammalian target of rapamycin pathways, are dependent on kallikrein related peptidase 4 (KLK4), whose expression is highly prostate enriched. Our results suggest that KLK4 has a central role in prostate cancer survival and that KLK4 silencing may have significant therapeutic efficacy.<\/jats:p>","DOI":"10.1073\/pnas.1304318110","type":"journal-article","created":{"date-parts":[[2013,6,25]],"date-time":"2013-06-25T04:20:05Z","timestamp":1372134005000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":58,"title":["Molecular circuit involving KLK4 integrates androgen and mTOR signaling in prostate cancer"],"prefix":"10.1073","volume":"110","author":[{"given":"Yang","family":"Jin","sequence":"first","affiliation":[{"name":"Department of Biosciences, University of Oslo, 0316 Oslo, Norway;"}]},{"given":"Su","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Biosciences, University of Oslo, 0316 Oslo, Norway;"}]},{"given":"Martina","family":"Tesikova","sequence":"additional","affiliation":[{"name":"Department of Biosciences, University of Oslo, 0316 Oslo, Norway;"}]},{"given":"Ling","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biosciences, University of Oslo, 0316 Oslo, Norway;"}]},{"given":"Alexandr","family":"Kristian","sequence":"additional","affiliation":[{"name":"Department of Tumor Biology,"}]},{"given":"Gunhild M.","family":"M\u00e6landsmo","sequence":"additional","affiliation":[{"name":"Department of Tumor Biology,"}]},{"given":"Haiying","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Biosciences, University of Oslo, 0316 Oslo, Norway;"}]},{"given":"Tianzhou","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biosciences, University of Oslo, 0316 Oslo, Norway;"}]},{"given":"Carmen","family":"Jer\u00f3nimo","sequence":"additional","affiliation":[{"name":"Genetics Department and Research Center, Portuguese Oncology Institute, 4200-072 Porto, Portugal;"},{"name":"Department of Pathology and Genetics, Biomedical Sciences Institute, University of Porto, 4200-072 Porto, Portugal; and"}]},{"given":"Manuel R.","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Genetics Department and Research Center, Portuguese Oncology Institute, 4200-072 Porto, Portugal;"},{"name":"Department of Pathology and Genetics, Biomedical Sciences Institute, University of Porto, 4200-072 Porto, Portugal; and"}]},{"given":"Erkan","family":"Yuca","sequence":"additional","affiliation":[{"name":"Department of Experimental Therapeutics and"}]},{"given":"Ibrahim","family":"Tekedereli","sequence":"additional","affiliation":[{"name":"Department of Experimental Therapeutics and"}]},{"given":"Kivanc","family":"Gorgulu","sequence":"additional","affiliation":[{"name":"Department of Experimental Therapeutics and"}]},{"given":"Neslihan","family":"Alpay","sequence":"additional","affiliation":[{"name":"Department of Experimental Therapeutics and"}]},{"given":"Anil K.","family":"Sood","sequence":"additional","affiliation":[{"name":"Department of Gynecological Oncology, MD Anderson Cancer Center, Houston, TX 77030"}]},{"given":"Gabriel","family":"Lopez-Berestein","sequence":"additional","affiliation":[{"name":"Department of Experimental Therapeutics and"}]},{"given":"H\u00e5vard E.","family":"Danielsen","sequence":"additional","affiliation":[{"name":"Center for Cancer Biomedicine, and"},{"name":"Institute for Medical Informatics, Oslo University Hospital, 0310 Oslo, Norway;"}]},{"given":"Bulent","family":"Ozpolat","sequence":"additional","affiliation":[{"name":"Department of Experimental Therapeutics and"}]},{"given":"Fahri","family":"Saatcioglu","sequence":"additional","affiliation":[{"name":"Department of Biosciences, University of Oslo, 0316 Oslo, Norway;"},{"name":"Institute for Medical Informatics, Oslo University Hospital, 0310 Oslo, Norway;"}]}],"member":"341","published-online":{"date-parts":[[2013,6,24]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.20107"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.20927"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2011.04.008"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6601127"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2011.05.006"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2402"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2008.07.005"},{"key":"e_1_3_3_8_2","first-page":"1008","article-title":"Disruption of androgen receptor function inhibits proliferation of androgen-refractory prostate cancer cells","volume":"62","author":"Zegarra-Moro OL","year":"2002","unstructured":"OL Zegarra-Moro, LJ Schmidt, H Huang, DJ Tindall, Disruption of androgen receptor function inhibits proliferation of androgen-refractory prostate cancer cells. 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