American Association for Cancer Research
00085472can124384-sup-fig3.pdf (879.31 kB)

Supplementary Figure 3 from Canonical Wnt Signaling Is Required for Pancreatic Carcinogenesis

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journal contribution
posted on 2023-03-30, 21:28 authored by Yaqing Zhang, John P. Morris, Wei Yan, Heather K. Schofield, Austin Gurney, Diane M. Simeone, Sarah E. Millar, Timothy Hoey, Matthias Hebrok, Marina Pasca di Magliano

PDF file - 879K, Supplemental Figure 3. PAS, Gomori Trichrome and Claudin18 IHC staining in KC and KDC pancreas.



Wnt ligand expression and activation of the Wnt/β-catenin pathway have been associated with pancreatic ductal adenocarcinoma, but whether Wnt activity is required for the development of pancreatic cancer has remained unclear. Here, we report the results of three different approaches to inhibit the Wnt/β-catenin pathway in a established transgenic mouse model of pancreatic cancer. First, we found that β-catenin null cells were incapable of undergoing acinar to ductal metaplasia, a process associated with development of premalignant pancreatic intraepithelial neoplasia lesions. Second, we addressed the specific role of ligand-mediated Wnt signaling through inducible expression of Dkk1, an endogenous secreted inhibitor of the canonical Wnt pathway. Finally, we targeted the Wnt pathway with OMP-18R5, a therapeutic antibody that interacts with multiple Frizzled receptors. Together, these approaches showed that ligand-mediated activation of the Wnt/β-catenin pathway is required to initiate pancreatic cancer. Moreover, they establish that Wnt signaling is also critical for progression of pancreatic cancer, a finding with potential therapeutic implications. Cancer Res; 73(15); 4909–22. ©2013 AACR.