Metabolic ProcessARDNA licensing factor for AR. Frequently occupies regions in enhancers with DNA recognition elements close to AR AREFrom Entrez Gene: The protein encoded by this gene is a trypsin inhibitor, which is secreted from pancreatic acinar cells into pancreatic juice. It is thought to function in the prevention of trypsin-catalyzed premature activation of zymogens within the pancreas and the pancreatic duct. Mutations in this gene are associated with hereditary pancreatitis and tropical calcific pancreatitisAssociation with Prostate Cancer - Chinnaiyan Lab Cancer Cell Paper - ETS gene fusions have been characterized in a majority of prostate cancers; however, the key molecular alterations in ETS-negative cancers are unclear. Here we used an outlier meta-analysis (meta-COPA) to identify SPINK1 outlier expression exclusively in a subset of ETS rearrangement-negative cancers (∼10% of total cases). We validated the mutual exclusivity of SPINK1 expression and ETS fusion status, demonstrated that SPINK1 outlier expression can be detected noninvasively in urine, and observed that SPINK1 outlier expression is an independent predictor of biochemical recurrence after resection. We identified the aggressive 22RV1 cell line as a SPINK1 outlier expression model and demonstrate that SPINK1 knockdown in 22RV1 attenuates invasion, suggesting a functional role in ETS rearrangement-negative prostate cancers.d2aAROncogenePhosphorylatedPhosphrylatedTumor supressorOncogeneFusion partner with TMPRSS2 in about 40% of prostate cancersFusion partner with TMPRSS2 in about 40% of prostate cancersDNA licensing factor for AR. Frequently occupies regions in enhancers with DNA recognition elements close to AR AREInterim Symbol: Dock1 predicted and Name: dedicator of cyto-kinesis 1 (predicted)Son of sevenless homolog 1 (Drosophila) (predicted)From Entrez Gene: The protein encoded by this gene is a trypsin inhibitor, which is secreted from pancreatic acinar cells into pancreatic juice. It is thought to function in the prevention of trypsin-catalyzed premature activation of zymogens within the pancreas and the pancreatic duct. Mutations in this gene are associated with hereditary pancreatitis and tropical calcific pancreatitisAssociation with Prostate Cancer - Chinnaiyan Lab Cancer Cell Paper - ETS gene fusions have been characterized in a majority of prostate cancers; however, the key molecular alterations in ETS-negative cancers are unclear. Here we used an outlier meta-analysis (meta-COPA) to identify SPINK1 outlier expression exclusively in a subset of ETS rearrangement-negative cancers (∼10% of total cases). We validated the mutual exclusivity of SPINK1 expression and ETS fusion status, demonstrated that SPINK1 outlier expression can be detected noninvasively in urine, and observed that SPINK1 outlier expression is an independent predictor of biochemical recurrence after resection. We identified the aggressive 22RV1 cell line as a SPINK1 outlier expression model and demonstrate that SPINK1 knockdown in 22RV1 attenuates invasion, suggesting a functional role in ETS rearrangement-negative prostate cancers.d2aNo LigandNo LigandAR Activated TranscriptionDashed line here to indicate fusion partnerType your comment herePHOSPHORYLATIONc92e82AR Activated TranscriptionAR Activated TranscriptionAR Activated TranscriptionAR Activated TranscriptionAR Activated TranscriptionAR Activated TranscriptionDashed line here to indicate fusion partnerType your comment hereAR Activated TranscriptionPHOSPHORYLATIONprostate cancer pathwayPW:0000609Pathway Ontologyprostate cancerDOID:10283Disease21544242PubMedMiR-21 induced angiogenesis through AKT and ERK activation and HIF-1α expression.PLoS One2011Liu LZLi CChen QJing YCarpenter RJiang YKung HFLai LJiang BH18538735PubMedThe role of SPINK1 in ETS rearrangement-negative prostate cancers.Cancer Cell2008Tomlins SARhodes DRYu JVarambally SMehra RPerner SDemichelis FHelgeson BELaxman BMorris DSCao QCao XAndrén OFall KJohnson LWei JTShah RBAl-Ahmadie HEastham JAEggener SEFine SWHotakainen KStenman UHTsodikov AGerald WLLilja HReuter VEKantoff PWScardino PTRubin MABjartell ASChinnaiyan AM21317927PubMedMicroRNA-21 targets tumor suppressor genes ANP32A and SMARCA4.Oncogene2011Schramedei KMörbt NPfeifer GLäuter JRosolowski MTomm JMvon Bergen MHorn FBrocke-Heidrich K