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

Research output: Contribution to journalArticle

123 Scopus citations

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 languageEnglish (US)
Pages (from-to)76-82
Number of pages7
JournalInternational Journal of Cancer
Volume91
Issue number1
DOIs
StatePublished - Jan 1 2001

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    McEarchern, J. A., Kobie, J. J., Mack, V., Wu, R. S., Meade-Tollin, L., Arteaga, C. L., Dumont, N., Besselsen, D., Seftor, E., Hendrix, M. J. C., Katsanis, E., & Akporiaye, E. T. (2001). Invasion and metastasis of a mammary tumor involves TGF-β signaling. International Journal of Cancer, 91(1), 76-82. https://doi.org/10.1002/1097-0215(20010101)91:1<76::AID-IJC1012>3.0.CO;2-8