Transforming growth factor-beta in cancer and metastasis

Cancer Metastasis Rev. 2006 Sep;25(3):435-57. doi: 10.1007/s10555-006-9006-2.


Transforming growth factor-beta (TGF-beta) is a multifunctional regulatory polypeptide that is the prototypical member of a large family of cytokines that controls many aspects of cellular function, including cellular proliferation, differentiation, migration, apoptosis, adhesion, angiogenesis, immune surveillance, and survival. The actions of TGF-beta are dependent on several factors including cell type, growth conditions, and the presence of other polypeptide growth factors. One of the biological effects of TGF-beta is the inhibition of proliferation of most normal epithelial cells using an autocrine mechanism of action, and this suggests a tumor suppressor role for TGF-beta. Loss of autocrine TGF-beta activity and/or responsiveness to exogenous TGF-beta appears to provide some epithelial cells with a growth advantage leading to malignant progression. This suggests a pro-oncogenic role for TGF-beta in addition to its tumor suppressor role. During the early phase of epithelial tumorigenesis, TGF-beta inhibits primary tumor development and growth by inducing cell cycle arrest and apoptosis. In late stages of tumor progression when tumor cells become resistant to growth inhibition by TGF-beta due to inactivation of the TGF-beta signaling pathway or aberrant regulation of the cell cycle, the role of TGF-beta becomes one of tumor promotion. Resistance to TGF-beta-mediated inhibition of proliferation is frequently observed in multiple human cancers, as are various alterations in the complex TGF-beta signaling and cell cycle pathways. TGF-beta can exert effects on tumor and stromal cells as well as alter the responsiveness of tumor cells to TGF-beta to stimulate invasion, angiogenesis, and metastasis, and to inhibit immune surveillance. Because of the dual role of TGF-beta as a tumor suppressor and pro-oncogenic factor, members of the TGF-beta signaling pathway are being considered as predictive biomarkers for progressive tumorigenesis, as well as molecular targets for prevention and treatment of cancer and metastasis.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Disease Progression
  • Humans
  • Neoplasm Metastasis*
  • Neoplasms / drug therapy
  • Neoplasms / metabolism*
  • Neoplasms / pathology*
  • Receptors, Transforming Growth Factor beta / antagonists & inhibitors
  • Transforming Growth Factor beta / antagonists & inhibitors
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / physiology*
  • Tumor Suppressor Proteins / antagonists & inhibitors
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / physiology*


  • Antineoplastic Agents
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta
  • Tumor Suppressor Proteins