Invasion and metastasis of a mammary tumor involves TGF-β signaling

Julie A. McEarchern, James J. Kobie, Vivian Mack, Rita S. Wu, Linda Meade-Tollin, Carlos L. Arteaga, Nancy Dumont, David Besselsen, Elisabeth Seftor, Mary J.C. Hendrix, Emmanuel Katsanis, Emmanuel T. Akporiaye*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

127 Scopus citations


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 languageEnglish (US)
Pages (from-to)76-82
Number of pages7
JournalInternational Journal of Cancer
Issue number1
StatePublished - Jan 1 2001


  • 4T1
  • Mammary cancer
  • Metastasis
  • Smad
  • TGF-β

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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