WNT Ligand Dependencies in Pancreatic Cancer

Kristina Y Aguilera; David W Dawson

doi:10.3389/fcell.2021.671022

WNT Ligand Dependencies in Pancreatic Cancer

Front Cell Dev Biol. 2021 Apr 28:9:671022. doi: 10.3389/fcell.2021.671022. eCollection 2021.

Authors

Kristina Y Aguilera¹, David W Dawson^{1

2}

Affiliations

¹ Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles, CA, United States.
² Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at University of California, Los Angeles, CA, United States.

Abstract

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.

Keywords: FZD5; PORCN; R-spondin; RNF43; WNT/β-catenin signaling; WNT7B; intraductal papillary mucinous neoplasms; pancreatic ductal adenocarcinoma.

Publication types

Review

Abstract

Publication types

Grants and funding