Alterations in components of the TGF-beta superfamily signaling pathways in human cancer

Cytokine Growth Factor Rev. Feb-Apr 2006;17(1-2):41-58. doi: 10.1016/j.cytogfr.2005.09.009. Epub 2005 Nov 23.

Abstract

Signaling by transforming growth factor-beta (TGF-beta) superfamily ligands to the nucleus is mediated by type I and type II receptors and the intracellular signal transducers, the Smads. Alteration of some of the components of these pathways has been observed in human tumors. These alterations can be deletions or mutations, or downregulation of components that act positively in the pathway, or alternatively, amplification or overexpression of inhibitors of the pathways. The selection of these alterations during tumor progression and their correlation with clinical outcomes, such as survival, risk of recurrence after tumor resection or tendency for metastatic spread, suggest that many are involved in tumor progression. Here, we review the genetic alterations and epigenetic modifications that occur in different components of the TGF-beta superfamily signaling pathways in human tumors and we discuss their correlation with clinical outcome. The evidence suggests that not all alterations of the TGF-beta superfamily signaling pathway components in human cancer have an equivalent effect on tumor progression and we discuss what implications this has for our understanding of the role of TGF-beta signaling in human cancer.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Epigenesis, Genetic / physiology
  • Humans
  • Multigene Family / genetics
  • Multigene Family / physiology*
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Receptors, Transforming Growth Factor beta / genetics
  • Receptors, Transforming Growth Factor beta / physiology*
  • Signal Transduction / genetics
  • Signal Transduction / physiology*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta / physiology*

Substances

  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta