Reduction in Smad2/3 Signaling Enhances Tumorigenesis but Suppresses Metastasis of Breast Cancer Cell Lines

Fang Tian, Stacey Da Costa Byfield, W. Tony Parks, Stephen Yoo, Angelina Felici, Binwu Tang, Ester Piek, Lalage M. Wakefield, Anita B. Roberts*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

152 Scopus citations

Abstract

The role of transforming growth factor β in breast cancer is controversial with tumor suppressor and pro-oncogenic activities having been demonstrated. To address whether the same or different signal transduction pathways mediate these opposing activities, we manipulated the Smad2/3 signaling pathway in cells of common origin but differing degrees of malignancy derived from MCF10A human breast cells. We show that interference with endogenous Smad2/3 signaling enhances the malignancy of xenografted tumors of premalignant and well-differentiated tumor cells but strongly suppresses lung metastases of more aggressive carcinoma cells after tail vein injection. Overexpression of Smad3 in the same cells has opposite effects. The data demonstrate that the Smad2/3 signaling pathway mediates tumor suppressor and prometastatic signals, depending on the cellular context.

Original languageEnglish (US)
Pages (from-to)8284-8292
Number of pages9
JournalCancer Research
Volume63
Issue number23
StatePublished - Dec 1 2003

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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