TGF-beta signaling: a tale of two responses

J Cell Biochem. 2007 Oct 15;102(3):593-608. doi: 10.1002/jcb.21501.


Transforming growth factor-beta (TGF-beta) regulates a wide variety of cellular processes including cell growth, apoptosis, differentiation, migration, and extracellular matrix production among others. The canonical signaling pathway induced by the TGF-beta receptor complex involves the phosphorylation of Smad proteins which upon activation accumulate in the nucleus and regulate transcription. Interestingly, the cellular response to TGF-beta can be extremely variable depending on the cell type and stimulation context. TGF-beta causes epithelial cells to undergo growth arrest and apoptosis, responses which are critical to suppressing carcinogenesis, whereas it can also induce epithelial-mesenchymal transition and mediate fibroblast activation, responses implicated in promoting carcinogenesis and fibrotic diseases. However, TGF-beta induces all these responses via the same receptor complex and Smad proteins. To address this apparent paradox, during the last few years a number of additional signaling pathways have been identified which potentially regulate the different cellular responses to TGF-beta. The identification of these signaling pathways has shed light onto the mechanisms whereby Smad and non-Smad pathways collaborate to induce a particular cellular phenotype. In this article, we review TGF-beta signaling in epithelial cells and fibroblasts with a focus on understanding the mechanisms of TGF-beta versatility.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis
  • Biochemistry / methods
  • Enzyme Activation
  • Epithelium / metabolism
  • Fibroblasts / metabolism
  • Humans
  • Mesoderm / metabolism
  • Models, Biological
  • Oncogenes
  • Phenotype
  • Signal Transduction*
  • Smad Proteins / metabolism
  • Transforming Growth Factor beta / metabolism*


  • Smad Proteins
  • Transforming Growth Factor beta