The Role of SncN and Ski in Mammary Epithelial Cell Transformation
Abstract
Although the growth inhibitory effects of TGFbeta play an important role in suppressing tumor cell proliferation early in tumorigenesis, TGFbeta signaling also promotes malignant progression. SnoN and Ski negatively regulate TGFbeta signaling by repressing the activity of the Smad proteins that act as effectors of the TGFbeta receptor kinase complex to regulate expression of most TGFbeta target genes. SnoN and Ski possess pro-oncogenic activity that promotes anchorage-independent growth of avian embryo fibroblasts. Here we confirm that expression of SnoN is elevated in human cancer cells and demonstrate that up regulation of SnoN is necessary for the loss of anti-proliferative responses to TGFbeta in two cancer cell lines. In addition, SnoN-deficient cancer cells are unable to undergo anchorage-independent growth or form tumors in nude mice. In contrast to these tumor-promoting effects of SnoN, we also show that SnoN can exert negative effects on cancer cell progression by inhibiting epithelial-to-mesenchymal transition (EMT). Cancer cells with reduced expression of SnoN exhibit increased motility, loss of cell adhesions, elevated stress fiber formation, and increased protease activity, and enhanced metastatic potential. Thus, SnoN possesses a dual role in epithelial cell tumorigenesis by both promoting the growth of tumor cells and suppressing cancer cell progression to a more invasive phenotype.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2005
- Accession Number
- ADA452549
Entities
People
- Ariel R. Krakowski
Organizations
- University of California, Berkeley