TGF-beta and cancer

Microbes Infect. 1999 Dec;1(15):1327-47. doi: 10.1016/s1286-4579(99)00251-8.


The relationships between transforming growth factor-beta (TGF-beta) and cancer are varied and complex. The paradigm that is emerging from the experimental evidence accumulated over the past decade or so is that TGF-beta can play two different and opposite roles with respect to the process of malignant progression. During early stages of carcinogenesis, TGF-beta acts predominantly as a potent tumor suppressor and may mediate the actions of chemopreventive agents such as retinoids and nonsteroidal anti-estrogens. However, at some point during the development and progression of malignant neoplasms, bioactive TGF-betas make their appearance in the tumor microenvironment and the tumor cells escape from TGF-beta-dependent growth arrest. In many cases, this resistance to TGF-beta is the consequence of loss or mutational inactivation of the genes that encode signaling intermediates. These include the types I and II TGF-beta receptors, as well as receptor-associated and common-mediator Smads. The stage of tumor development or progression at which TGF-beta-resistant clones come to dominate the tumor cell population in different types of neoplasm remains to be defined. The phenotypic switch from TGF-beta-sensitivity to TGF-beta-resistance that occurs during carcinogenesis has several important implications for cancer prevention and treatment.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Humans
  • Mice
  • Neoplasms / immunology*
  • Signal Transduction
  • Trans-Activators / metabolism
  • Transforming Growth Factor beta / physiology*


  • Trans-Activators
  • Transforming Growth Factor beta