1. The loss of tuberin promotes cell invasion through the ß-catenin pathway.
- Author
-
Barnes EA, Kenerson HL, Mak BC, and Yeung RS
- Subjects
- Animals, Caspase 3 metabolism, Cell Adhesion, Cell Line, Cell Proliferation, Cell Survival, Contact Inhibition, Fibroblasts enzymology, Fibroblasts pathology, Humans, Kidney Neoplasms metabolism, Kidney Neoplasms pathology, Lymphangioleiomyomatosis metabolism, Lymphangioleiomyomatosis pathology, Matrix Metalloproteinase 7 metabolism, Mutant Proteins metabolism, Rats, Transcription, Genetic, Tuberous Sclerosis Complex 2 Protein, Tumor Suppressor Proteins deficiency, beta Catenin genetics, Cell Movement, Signal Transduction, Tumor Suppressor Proteins metabolism, beta Catenin metabolism
- Abstract
Mutations in the tumor suppressor tuberin (TSC2) are a common factor in the development of lymphangioleiomyomatosis (LAM). LAM is a cystic lung disease that is characterized by the infiltration of smooth muscle-like cells into the pulmonary parenchyma. The mechanism by which the loss of tuberin promotes the development of LAM has yet to be elucidated, although several lines of evidence suggest it is due to the metastasis of tuberin-deficient cells. Here we show that tuberin-null cells become nonadherent and invasive. These nonadherent cells express cleaved forms of β-catenin. In reporter assays, the β-catenin products are transcriptionally active and promote MMP7 expression. Invasion by the tuberin-null cells is mediated by MMP7. Examination of LAM tissues shows the expression of cleaved β-catenin products and MMP7 consistent with a model that tuberin-deficient cells acquire invasive properties through a β-catenin-dependent mechanism, which may underlie the development of LAM.
- Published
- 2010
- Full Text
- View/download PDF