TY - JOUR
T1 - Common activation of canonical Wnt signaling in pancreatic adenocarcinoma
AU - Pasca di Magliano, Marina
AU - Biankin, Andrew V.
AU - Heiser, Patrick W.
AU - Cano, David A.
AU - Gutierrez, Pedro J.A.
AU - Deramaudt, Therese
AU - Segara, Davendra
AU - Dawson, Amanda C.
AU - Kench, James G.
AU - Henshall, Susan M.
AU - Sutherland, Robert L.
AU - Dlugosz, Andrzej
AU - Rustgi, Anil K.
AU - Hebrok, Matthias
PY - 2007/11/7
Y1 - 2007/11/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=42649138943&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0001155
DO - 10.1371/journal.pone.0001155
M3 - Article
C2 - 17982507
AN - SCOPUS:42649138943
SN - 1932-6203
VL - 2
JO - PLoS ONE
JF - PLoS ONE
IS - 11
M1 - e1155
ER -
