Lunatic Fringe suppresses pancreatic cancer progression through inhibition of Notch signaling

• 作 者: ShubingZhang[1]Wen-ChengChung[2]
• 机 构: Cancer Institute,University of Mississippi Medical Center,Jackson,Mississippi,USA
• 出 处: 中国病理生理学会第十四届肿瘤专业委员会、第十五届免疫专业委员会联合学术会议
• 发表日期: 2014年期

　　Aim: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies in humans.In recent years,mouse models recapitulating a spectrum of pathologic changes in PDAC have been generated by the mimicry of genetic alterations found in human patients.Genetic analyses using animal models identified additional genes and signals involved in PDAC pathogenesis.Among those,the Notch signaling pathway was found up-regulated in both initiation and progression of the disease.In fact,nuclear NOTCH3 and HEY1 expression was significantly associated with reduced survival in PDAC patients.However,the Notch signaling pathway may play complex roles through multiple Notch receptors and ligands in different cell types of the pancreas.Interestingly,Notch signaling is regulated by the Fringe family of 3N-acteylglucosaminyl-transferases that modify EGF repeats in the extracellular domains of Notch receptors to control ligand-mediated activation.