Research Report 2010 - MDC

The tyrosine phosphatase Shp2 directs Neuregulin-1/ErbB signaling throughout Schwann cell developmentIn vivo analysis of Schwann cells associated with peripheral nerves in control and Wnt1-cre Shp2 fl/fl mice at the indicated developmental stagesusing (A,B) immunohistochemistry for BFABP (red) and neurofilament (NF, green), (C,D) in situ hybridization with a Sox10-specific probe, and (E,F)histological sections stained with hematoxylin and eosin. Note the reduced numbers of Schwann cells at Shp2 mutant peripheral nerves.In vitro analysis of the role of Shp2 during Schwann cell proliferation and migration. (G) Southern blot and (H) Western blot analyses after HTNcreinduced recombination in cultured Shp2 fl/fl Schwann cells. (I,J) Quantification of the Nrg1-induced proliferation and migration indicates strongreduction of both cellular responses in the absence of Shp2. Shown are the percentage of Schwann cells that incorporated BrdU, or the percentageof Schwann cells that migrated into the scratched area, using control and Shp2 ∆/∆ Schwann cells (HTN-cre-treated Shp2 fl/fl Schwann cells) in thepresence and absence of Nrg1. (K-L´) Migration of Schwann cells into a scratched area.sion and metastasis-free survival time of patients.BAMBI inhibits TGFβ signaling and increases migrationin colon cancer cells. In mice, overexpression of BAMBIcaused colon cancer cells to form tumors that metastasizedmore frequently to liver and lymph nodes thancontrol cancer cells. Thus BAMBI regulates colorectalcancer metastasis by connecting the Wnt/β-cateninand TGFβ signaling pathways. The metastatic expressionsignature we describe, along with BAMBI levels,may be used in prognosis in the future. Our data alsoshow that developmental signaling pathways act inhierarchies and cooperate in tumor cell migration, invasionand metastasis.Skin cancer stem cell maintenance is dependanton catenin signaling throughout Schwann celldevelopmentIlaria Malanchi, Deepika Kassen, Thomas Hussenet, JörgHuelsken (EPFL/ISREC Lausanne), Amparo Cano (CSIC-UAMMadrid) and Walter Birchmeier.Proper canonical Wnt signaling guides healthy developmentin many tissues, but defects play a role in tumors,as revealed by the analysis of loss- and gain-of functionmutations in β-catenin. The recently identified cancerstem cells and normal stem cells share many characteristics,like the capacity for self-renewal and differentiationand their dependence on a particular microenvi-84 Cancer Research