Mechanisms of the epithelial–mesenchymal transition by TGF-β
- 1 October 2009
- journal article
- review article
- Published by Future Medicine Ltd in Future Oncology
- Vol. 5 (8), 1145-1168
- https://doi.org/10.2217/fon.09.90
Abstract
The formation of epithelial cell barriers results from the defined spatiotemporal differentiation of stem cells into a specialized and polarized epithelium, a process termed mesenchymal–epithelial transition. The reverse process, epithelial–mesenchymal transition (EMT), is a metastable process that enables polarized epithelial cells to acquire a motile fibroblastoid phenotype. Physiological EMT also plays an essential role in promoting tissue healing, remodeling or repair in response to a variety of pathological insults. On the other hand, pathophysiological EMT is a critical step in mediating the acquisition of metastatic phenotypes by localized carcinomas. Although metastasis clearly is the most lethal aspect of cancer, our knowledge of the molecular events that govern its development, including those underlying EMT, remain relatively undefined. Transforming growth factor-β (TGF-β) is a multifunctional cytokine that oversees and directs all aspects of cell development, differentiation and homeostasis, as well as suppresses their uncontrolled proliferation and transformation. Quite dichotomously, tumorigenesis subverts the tumor suppressing function of TGF-β, and in doing so, converts TGF-β to a tumor promoter that stimulates pathophysiological EMT and metastasis. It therefore stands to reason that determining how TGF-β induces EMT in developing neoplasms will enable science and medicine to produce novel pharmacological agents capable of preventing its ability to do so, thereby improving the clinical course of cancer patients. Here we review the cellular, molecular and microenvironmental mechanisms used by TGF-β to mediate its stimulation of EMT in normal and malignant cells.Keywords
This publication has 149 references indexed in Scilit:
- TRAF6 Mediates Smad-Independent Activation of JNK and p38 by TGF-βMolecular Cell, 2008
- NCAM-induced focal adhesion assembly: a functional switch upon loss of E-cadherinThe EMBO Journal, 2008
- A reciprocal repression between ZEB1 and members of the miR‐200 family promotes EMT and invasion in cancer cellsEMBO Reports, 2008
- The Epithelial-Mesenchymal Transition Generates Cells with Properties of Stem CellsCell, 2008
- Abrogation of TGFβ Signaling in Mammary Carcinomas Recruits Gr-1+CD11b+ Myeloid Cells that Promote MetastasisCancer Cell, 2008
- Combinatorial activation of FAK and AKT by transforming growth factor-β1 confers an anoikis-resistant phenotype to myofibroblastsCellular Signalling, 2007
- Fibrosis and cancer: Do myofibroblasts come also from epithelial cells via EMT?Journal of Cellular Biochemistry, 2007
- Nuclear factor-κB in cancer development and progressionNature, 2006
- Generation of a functional mammary gland from a single stem cellNature, 2006
- The Hallmarks of CancerCell, 2000