Abstract
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) |
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Pages (from-to) | 76-82 |
Number of pages | 7 |
Journal | International Journal of Cancer |
Volume | 91 |
Issue number | 1 |
DOIs | |
State | Published - Jan 1 2001 |
Keywords
- 4T1
- Mammary cancer
- Metastasis
- Smad
- TGF-β
ASJC Scopus subject areas
- Oncology
- Cancer Research