Abstract
Pancreatic ductal adenocarcinoma (PDA) is an extremely aggressive malignancy, which carries a dismal prognosis. Activating mutations of the Kras gene are common to the vast majority of human PDA. In addition, recent studies have demonstrated that embryonic signaling pathway such as Hedgehog and Notch are inappropriately upregulated in this disease. The role of another embryonic signaling pathway, namely the canonical Wnt cascade, is still controversial. Here, we use gene array analysis as a platform to demonstrate general activation of the canonical arm of the Wnt pathway in human PDA. Furthermore, we provide evidence for Wnt activation in mouse models of pancreatic cancer. Our results also indicate that Wnt signaling might be activated downstream of Hedgehog signaling, which is an early event in PDA evolution. Wnt inhibition blocked proliferation and induced apoptosis of cultured adenocarcinoma cells, thereby providing evidence to support the development of novel therapeutical strategies for Wnt inhibition in pancreatic adenocarcinoma.
Highlights
Pancreatic ductal adenocarcinoma (PDA) is the fourth leading cause of cancer death in Western societies
There is compelling histopathological and molecular evidence to support the evolution of PDA through a series of non-invasive duct lesions called pancreatic intraepithelial neoplasia (PanIN) [2]
Progression of PanIN lesion is associated with molecular aberrations that increase in frequency and correlate with advancing cellular atypia from early stages to invasive cancer [3,4]
Summary
Pancreatic ductal adenocarcinoma (PDA) is the fourth leading cause of cancer death in Western societies. Activation of the Wnt signaling pathway in pancreatic cancer has remained controversial [24] and functional studies addressing a potential contribution of Wnt signaling to PDA development and progression are currently missing. Support for this notion comes from studies in Pdx-Cre;KrasG12D transgenic mice in which expression of the prevalent KrasG12D mutation in pancreatic epithelial cells results in the formation of tumors that resemble human PDA [31].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
