Tumor-promoting functions of transforming growth factor-β in progression of cancer

Ups J Med Sci. 2012 May;117(2):143-52. doi: 10.3109/03009734.2011.638729. Epub 2011 Nov 24.

Abstract

Transforming growth factor-β (TGF-β) elicits both tumor-suppressive and tumor-promoting functions during cancer progression. Here, we describe the tumor-promoting functions of TGF-β and how these functions play a role in cancer progression. Normal epithelial cells undergo epithelial-mesenchymal transition (EMT) through the action of TGF-β, while treatment with TGF-β and fibroblast growth factor (FGF)-2 results in transdifferentiation into activated fibroblastic cells that are highly migratory, thereby facilitating cancer invasion and metastasis. TGF-β also induces EMT in tumor cells, which can be regulated by oncogenic and anti-oncogenic signals. In addition to EMT promotion, invasion and metastasis of cancer are facilitated by TGF-β through other mechanisms, such as regulation of cell survival, angiogenesis, and vascular integrity, and interaction with the tumor microenvironment. TGF-β also plays a critical role in regulating the cancer-initiating properties of certain types of cells, including glioma-initiating cells. These findings thus may be useful for establishing treatment strategies for advanced cancer by inhibiting TGF-β signaling.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation
  • Disease Progression
  • Epithelial-Mesenchymal Transition
  • Fibroblast Growth Factor 2 / physiology
  • Humans
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasms / pathology*
  • Neoplasms / physiopathology
  • Signal Transduction
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta / physiology*

Substances

  • Transforming Growth Factor beta
  • Fibroblast Growth Factor 2