Several studies have correlated escape from TGF-β-mediated cell cycle arrest with the tumorigenic phenotype. Most often, this escape from growth control has been linked to dysfunctional TGF-β receptors or defects in the TGF-β-mediated SMAD signaling pathway. In this report, we found that highly metastatic 4TI mammary carcinoma cells express functional TGF-β receptors capable of initiating SMAD-mediated transcription, yet are not growth inhibited by TGF-βI. We further observed that TGF-β directly contributes to the metastatic behavior of this cell line. Exposure to TGF-β caused 4TI cells to undergo morphological changes associated with the metastatic phenotype and invade more readily through collagen coated matrices. Furthermore, expression of a dominant negative truncated type II receptor diminished TGF-β signaling and significantly restricted the ability of 4TI cells to establish distant metastases. Our results suggest that regardless of 4TI resistance to TGF-β-mediated growth inhibition, TGF-β signaling is required for tumor invasion and metastases formation. (C) 2001 Wiley-Liss, Inc.
|Original language||English (US)|
|Number of pages||7|
|Journal||International Journal of Cancer|
|State||Published - Jan 1 2001|
- Mammary cancer
ASJC Scopus subject areas
- Cancer Research