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

121 Citations (Scopus)

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

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Breast Neoplasms
Neoplasm Metastasis
Growth
Phenotype
Cell Cycle Checkpoints
Collagen
Cell Line
Neoplasms

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

McEarchern, J. A., Kobie, J. J., Mack, V., Wu, R. S., Meade-Tollin, L., Arteaga, C. L., ... 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

Invasion and metastasis of a mammary tumor involves TGF-β signaling. / McEarchern, Julie A.; Kobie, James J.; Mack, Vivian; Wu, Rita S.; Meade-Tollin, Linda; Arteaga, Carlos L.; Dumont, Nancy; Besselsen, David; Seftor, Elisabeth; Hendrix, Mary J C; Katsanis, Emmanuel; Akporiaye, Emmanuel T.

In: International Journal of Cancer, Vol. 91, No. 1, 01.01.2001, p. 76-82.

Research output: Contribution to journalArticle

McEarchern, JA, Kobie, JJ, Mack, V, Wu, RS, Meade-Tollin, L, Arteaga, CL, Dumont, N, Besselsen, D, Seftor, E, Hendrix, MJC, Katsanis, E & Akporiaye, ET 2001, 'Invasion and metastasis of a mammary tumor involves TGF-β signaling', International Journal of Cancer, vol. 91, no. 1, pp. 76-82. https://doi.org/10.1002/1097-0215(20010101)91:1<76::AID-IJC1012>3.0.CO;2-8
McEarchern, Julie A. ; Kobie, James J. ; Mack, Vivian ; Wu, Rita S. ; Meade-Tollin, Linda ; Arteaga, Carlos L. ; Dumont, Nancy ; Besselsen, David ; Seftor, Elisabeth ; Hendrix, Mary J C ; Katsanis, Emmanuel ; Akporiaye, Emmanuel T. / Invasion and metastasis of a mammary tumor involves TGF-β signaling. In: International Journal of Cancer. 2001 ; Vol. 91, No. 1. pp. 76-82.
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