Journal
FEBS LETTERS
Volume 586, Issue 14, Pages 1959-1970Publisher
WILEY
DOI: 10.1016/j.febslet.2012.02.037
Keywords
Cancer stem cell; Epithelial-mesenchymal transition; MAPK; Metastasis; Smad; TGF beta
Funding
- Ludwig Institute for Cancer Research
- Swedish Cancer Society
- Swedish Research Council
- Network of Excellence ENFIN'' under the European Union
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Transforming growth factor-beta (TGF beta) suppresses tumor formation since it inhibits cell growth and promotes apoptosis. However, in advanced cancers TGF beta elicits tumor promoting effects through its ability to induce epithelial-mesenchymal transition (EMT) which enhances invasiveness and metastasis; in addition, TGF beta exerts tumor promoting effects on non-malignant cells of the tumor, including suppression of immune surveillance and stimulation of angiogenesis. TGF beta promotes EMT by transcriptional and posttranscriptional regulation of a group of transcription factors that suppresses epithelial features, such as expression of components of cell junctions and polarity complexes, and enhances mesenchymal features, such as production of matrix molecules and several cytokines and growth factors that stimulate cell migration. The EMT program has certain similarities with the stem cell program. Inducers and effectors of EMT are interesting targets for the development of improved diagnosis, prognosis and therapy of cancer. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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