Yes-associated protein(YAP)in pancreatic cancer:at the epicenter of a targetable signaling network associated with patient survival

作     者：Enrique Rozengurt James Sinnett-Smith Guido Eibl 

作者机构：Department of MedicineDavid Geffen School of MedicineUniversity of CaliforniaLos AngelesCA 9005USA CURE:Digestive Diseases Research CenterUniversity of CaliforniaLos AngelesCA 9005USA Molecular Biology InstituteUniversity of CaliforniaLos AngelesCA 9005USA Department of SurgeryDavid Geffen School of MedicineUniversity of CaliforniaLos AngelesCA 9005USA 

出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)

年 卷 期：2018年第3卷第1期

页      面：226-235页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：E.R.is supported by NIH Grants P01CA163200,R01DK100405,and P30DK41301 by a Department of Veterans Affair Grant 1I01BX001473 funds from the endowed Ronald S.Hirschberg Chair of Pancreatic Cancer Research.G.E.is supported by P01CA163200 funds from the Hirschberg Foundation of Pancreatic Cancer Research.The funders had no role in the preparation of the manuscript 

主　　题：prevention cancer network 

摘      要：Pancreatic ductal adenocarcinoma(PDAC)is generally a fatal disease with no efficacious treatment *** of signaling mechanisms that will lead to the identification of novel targets for therapy and chemoprevention is urgently ***,we review the role of Yes-associated protein(YAP)and WW-domain-containing Transcriptional co-Activator with a PDZbinding motif(TAZ)in the development of *** oncogenic proteins are at the center of a signaling network that involves multiple upstream signals and downstream YAP-regulated *** also discuss the clinical significance of the YAP signaling network in PDAC using a recently published interactive open-access database(***/pathology)that allows genome-wide exploration of the impact of individual proteins on survival *** YAP/TEAD-regulated genes,including AJUBA,ANLN,AREG,ARHGAP29,AURKA,BUB1,CCND1,CDK6,CXCL5,EDN2,DKK1,FOSL1,FOXM1,HBEGF,IGFBP2,JAG1,NOTCH2,RHAMM,RRM2,SERP1,and ZWILCH,are associated with unfavorable survival of PDAC ***,components of AP-1 that synergize with YAP(FOSL1),growth factors(TGFα,EPEG,and HBEGF),a specific integrin(ITGA2),heptahelical receptors(P2Y2R,GPR87)and an inhibitor of the Hippo pathway(MUC1),all of which stimulate YAP activity,are associated with unfavorable survival of PDAC *** contrast,YAP inhibitory pathways(STRAD/LKB-1/AMPK,PKA/LATS,and TSC/mTORC1)indicate a favorable *** associations emphasize that the YAP signaling network correlates with poor survival of pancreatic cancer *** conclude that the YAP pathway is a major determinant of clinical aggressiveness in PDAC patients and a target for therapeutic and preventive strategies in this disease.