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closeReferee Comments: Referee 2 (Anne Grapin)
Posted by PLOS_ONE_Group on 14 Nov 2007 at 23:51 GMT
Reviewer 2's Review
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In this article, Marina Pasca di Magliano and co-workers report the unexpected observation that the Wnt pathway is activated and functionally important in pancreatic adenocarcinoma (PDA). Indeed, activation of the Wnt pathway is traditionally associated with other types of pancreatic cancers. The argument is logically and convincingly developed, showing firstly cytoplasmic beta catenin and activation of other Wnt targets in a large collection of human samples. Of importance, it is made clear that the levels of signalling are lower than those observed in colon cancer. The authors then show that the Wnt pathway is also activated in well validated models of PDA. To study the functional relevance of this pathway, the authors use multiple PDA cell lines. They demonstrate the activity of the pathway and compare it to the activity in a colon cancer cell line. They then use to methods to reduce the activity of the pathway to show that it reduces proliferation and increases apoptosis. Lastly, the authors have shown that the Shh pathway is important in PDA. They show that the Wnt pathway appears to function downstream of the Shh pathway (in vitro and in vivo) via an up-regulation of TCF4. Taken together, although the finding is surprising, the demonstration is convincing, often redundant and is therefore worth publishing.
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N.B. These are the general comments made by the reviewer when reviewing this paper in light of which the manuscript was revised. Specific points addressed during revision of the paper are not shown.