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Common activation of canonical wnt signaling in pancreatic adenocarcinoma


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.

Type Journal
ISBN 1932-6203 (Electronic)
Authors Pasca di Magliano, M.;Biankin, A. V.;Heiser, P. W.;Cano, D. A.;Gutierrez, P. J.;Deramaudt, T.;Segara, D.;Dawson, A. C.;Kench, J. G.;Henshall, S. M.;Sutherland, R. L.;Dlugosz, A.;Rustgi, A. K.;Hebrok, M. :
Publisher Name PLoS One
Published Date 2007-01-01
Published Volume 2
Published Issue 11
Published Pages e1155
Status Published in-print
URL link to publisher's version
OpenAccess link to author's accepted manuscript version