胰腺癌中的是相关蛋白（YAP）：位于与患者生存相关的可定向信号网络的震中。,Signal Transduction and Targeted Therapy

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胰腺癌中的是相关蛋白（YAP）：位于与患者生存相关的可定向信号网络的震中。
Signal Transduction and Targeted Therapy ( IF 40.8 ) Pub Date : 2018-04-20 , DOI: 10.1038/s41392-017-0005-2
Enrique Rozengurt _{1,

2,

3} , James Sinnett-Smith _{1,

2} , Guido Eibl _{2,

4}

Affiliation

胰腺导管腺癌（PDAC）通常是致命的疾病，没有有效的治疗方法。迫切需要阐明将导致鉴定治疗和化学预防新靶标的信号传导机制。在这里，我们回顾了是相关蛋白（YAP）和含WW域的转录共激活因子以及PDZ结合基序（TAZ）在PDAC发展中的作用。这些致癌蛋白位于包含多个上游信号和下游YAP调控基因的信号网络的中心。我们还使用最近发布的交互式开放访问数据库（www.proteinatlas.org/pathology）讨论了PDAC中的YAP信号网络的临床意义，该数据库允许在全基因组范围内探索单个蛋白质对生存结果的影响。多个YAP / TEAD调控基因，包括AJUBA，ANNL，AREG，ARHGAP29，AURKA，BUB1，CCND1，CDK6，CXCL5，EDN2，DKK1，FOSL1，FOXM1，HBEGF，IGFBP2，JAG1，NOTCH2，RHAMM，RRM2，SERP1 ZWILCH与PDAC患者的不良生存有关。同样，与YAP（FOSL1），生长因子（TGFα，EPEG和HBEGF），特异性整联蛋白（ITGA2），七螺旋受体（P2Y2R，GPR87）和Hippo途径抑制剂（MUC1）协同作用的AP-1组分，所有刺激YAP活性的患者，都与PDAC患者的不良生存有关。相比之下，YAP抑制途径（STRAD / LKB-1 / AMPK，PKA / LATS和TSC / mTORC1）表明预后良好。这些关联强调，YAP信号网络与胰腺癌患者的不良生存相关。

"点击查看英文标题和摘要"

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

Pancreatic ductal adenocarcinoma (PDAC) is generally a fatal disease with no efficacious treatment modalities. Elucidation of signaling mechanisms that will lead to the identification of novel targets for therapy and chemoprevention is urgently needed. Here, we review the role of Yes-associated protein (YAP) and WW-domain-containing Transcriptional co-Activator with a PDZ-binding motif (TAZ) in the development of PDAC. These oncogenic proteins are at the center of a signaling network that involves multiple upstream signals and downstream YAP-regulated genes. We also discuss the clinical significance of the YAP signaling network in PDAC using a recently published interactive open-access database (www.proteinatlas.org/pathology) that allows genome-wide exploration of the impact of individual proteins on survival outcomes. Multiple 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 patients. Similarly, 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 patients. By contrast, YAP inhibitory pathways (STRAD/LKB-1/AMPK, PKA/LATS, and TSC/mTORC1) indicate a favorable prognosis. These associations emphasize that the YAP signaling network correlates with poor survival of pancreatic cancer patients. We 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.

更新日期：2019-05-16

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