Loss of TGF-β signaling in epithelial-derived tumors: Mechanisms and biological consequences

J. W. Freeman

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

The purpose of this article is to review current knowledge of the role that loss in transforming growth factor beta (TGF-β) signaling has on the tumorgenicity of epithelial derived tumors. The mechanisms responsible for loss in TGF-β signaling are also summarized. Loss in response to TGF-β is one of the hallmarks of tumor progression. Loss in TGF-β signaling provides cells with a selective growth advantage by diminishing the expression of cyclin-dependent kinase inhibitors, circumventing cell cycle checkpoints, and promoting cell survival The loss of TGF-β signaling is mediated by a variety of mechanisms. These include mutations that inactivate TGF-β receptors and Smads, expression of oncoproteins ski and sno that inactivate Smad complexes, over-expression of antagonistic Smads, and epigenetic events that down regulate TGF-β receptor expression. A further understanding of these mechanisms may lead to the development of therapeutic strategies that restore TGF-β signaling.

Original languageEnglish (US)
Pages (from-to)239-244
Number of pages6
JournalJournal of Clinical Ligand Assay
Volume23
Issue number3
StatePublished - Dec 1 2000

Keywords

  • Cancer
  • Cell cycle
  • Gene regulation
  • Growth regulation
  • Smads
  • TGF-β
  • TGF-β receptors
  • Tumorigenicity

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical

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