Journal
NATURE STRUCTURAL & MOLECULAR BIOLOGY
Volume 17, Issue 6, Pages 718-U90Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.1833
Keywords
-
Funding
- Swedish Cancer Society
- Wenner-Gren-Foundation
- Lars Hiertas Minne Foundation
- Karolinska Institutet
- Swedish Research Council
- US National Institutes of Health National Cancer Institute [UO1 CA105491]
- Swiss Bridge
Ask authors/readers for more resources
Synergism between the RAS and Hedgehog (HH) pathways has been suggested for carcinogenesis in the pancreas, lung and colon. We investigated the molecular cross-talk between RAS and HH signaling and found that, although mutant RAS induces or enhances SHH expression and favors paracrine HH signaling, it antagonizes autocrine HH signal transduction. Activated RAS can be found in primary cilia, the central organelle of HH signal transduction, but functions in a cilium-independent manner and interferes with Gli2 function and Gli3 processing. In addition, the cell-autonomous negative regulation of HH signal transduction involves the RAS effector molecule dual specificity tyrosine phosphorylated and regulated kinase 1B (DYRK1B). In line with a redirection of autocrine toward paracrine HH signaling by a KRAS-DYRK1B network, we find high levels of GLI1 expression restricted to the stromal compartment and not to SHH-expressing tumor cells in human pancreatic adenocarcinoma.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available