Loss of metal transcription factor-1 suppresses tumor growth through enhanced matrix deposition

Zishan A. Haroon, Khalid Amin, Peter Lichtlen, Barbara Sato, Nhung T. Huynh, Zhaohui Wang, Walter Schaffner, Brian J. Murphy

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Metal transcription factor-1 (MTF-1) is a ubiquitous transcriptional regulator and chromatin insulator with roles in cellular stress responses and embryonic development. The studies described herein establish for the first time the involvement of MTF-1 in tumor development. Genetically manipulated ros-transformed mouse embryonic fibroblasts (MEFs), wild-type (MTF-1 +/+), or nullizygous for MTF-1 (MTF-1-/-) were used to develop fibrosarcoma tumors. Loss of MTF-1 resulted in delayed tumor growth associated with increased matrix collagen deposition and reductions in vasculature density. Molecular consequences of MTF-1 loss include increased expression and activation of the transforming growth factor-β1 (TGF-β1) and tissue transglutaminase (tTG), two proteins with documented roles in the production and stabilization of extracellular matrix (ECM). Our findings support the hypothesis that MTF-1 enhances the ability of the developing tumor mass to evade fibrosis and scarring of the tumor, a critical step in tumor cell proliferation.

Original languageEnglish (US)
Pages (from-to)1176-1184
Number of pages9
JournalFASEB Journal
Volume18
Issue number11
DOIs
StatePublished - Aug 2004

Keywords

  • Fibrosis
  • MTF-1
  • Tumorigenesis

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