Aguilera Kristina Y, Dawson David W
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles, CA, United States.
Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at University of California, Los Angeles, CA, United States.
Front Cell Dev Biol. 2021 Apr 28;9:671022. doi: 10.3389/fcell.2021.671022. eCollection 2021.
WNT signaling promotes the initiation and progression of pancreatic ductal adenocarcinoma (PDAC) through wide-ranging effects on cellular proliferation, survival, differentiation, stemness, and tumor microenvironment. Of therapeutic interest is a genetically defined subset of PDAC known to have increased WNT/β-catenin transcriptional activity, growth dependency on WNT ligand signaling, and response to pharmacologic inhibitors of the WNT pathway. Here we review mechanisms underlying WNT ligand addiction in pancreatic tumorigenesis, as well as the potential utility of therapeutic approaches that functionally antagonize WNT ligand secretion or frizzled receptor binding.
WNT信号通路通过对细胞增殖、存活、分化、干性和肿瘤微环境产生广泛影响，促进胰腺导管腺癌（PDAC）的发生和发展。具有治疗意义的是一类基因定义的PDAC亚群，已知其WNT/β-连环蛋白转录活性增加，生长依赖于WNT配体信号传导，并且对WNT通路的药理抑制剂有反应。在此，我们综述了胰腺肿瘤发生过程中WNT配体成瘾的潜在机制，以及在功能上拮抗WNT配体分泌或卷曲受体结合的治疗方法的潜在效用。
