Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Oncogene. 2010 Apr 29;29(17):2540-9. doi: 10.1038/onc.2010.20. Epub 2010 Feb 15.

NF2-deficient cells depend on the Rac1-canonical Wnt signaling pathway to promote the loss of contact inhibition of proliferation.

Author information

  • 1Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.

Abstract

The neurofibromatosis type 2 (NF2) tumor suppressor gene encodes merlin, a membrane/cytoskeleton protein necessary for the maintenance of contact inhibition of growth in cells. Bi-allelic inactivation of NF2 is known to cause multiple cancers in both humans and mice. However, the mechanism through which merlin exerts its tumor-suppressive function remains obscure. In this report, we show that NF2 knockout mouse embryonic fibroblasts lost contact inhibition of cell proliferation and contained significantly increased canonical Wnt signaling. Inhibition of Rac1, the activity of which is inversely regulated by NF2, through the use of a dominant-negative mutant, small hairpin RNA or a small molecule inhibitor in NF2-deficient cells, was able to suppress elevated Wnt signals as shown by reduced activity of the T-cell factor 4 (TCF4) transcription factor. Dominant-negative TCF4 or Rac1 mutant, as well as a small molecule inhibition of Wnt, were able to curb NF2 deficiency-elicited cell proliferation at the confluent state. Thus, Rac1-mediated canonical Wnt signaling is essential for the loss of contact inhibition in NF2-deficient cells.

PMID:
20154721
[PubMed - indexed for MEDLINE]
PMCID:
PMC2861729
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Write to the Help Desk