| Literature DB >> 23453624 |
Stefan Eser1, Nina Reiff, Marlena Messer, Barbara Seidler, Kathleen Gottschalk, Melanie Dobler, Maren Hieber, Andreas Arbeiter, Sabine Klein, Bo Kong, Christoph W Michalski, Anna Melissa Schlitter, Irene Esposito, Alexander J Kind, Lena Rad, Angelika E Schnieke, Manuela Baccarini, Dario R Alessi, Roland Rad, Roland M Schmid, Günter Schneider, Dieter Saur.
Abstract
Oncogenic Kras activates a plethora of signaling pathways, but our understanding of critical Ras effectors is still very limited. We show that cell-autonomous phosphoinositide 3-kinase (PI3K) and 3-phosphoinositide-dependent protein kinase 1 (PDK1), but not Craf, are key effectors of oncogenic Kras in the pancreas, mediating cell plasticity, acinar-to-ductal metaplasia (ADM), and pancreatic ductal adenocarcinoma (PDAC) formation. This contrasts with Kras-driven non-small cell lung cancer, where signaling via Craf, but not PDK1, is an essential tumor-initiating event. These in vivo genetic studies together with pharmacologic treatment studies in models of human ADM and PDAC demonstrate tissue-specific differences of oncogenic Kras signaling and define PI3K/PDK1 as a suitable target for therapeutic intervention specifically in PDAC.Entities:
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Year: 2013 PMID： 23453624 DOI： 10.1016/j.ccr.2013.01.023
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743