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Actions of TGF-beta as tumor suppressor and pro-metastatic factor in human cancer
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Ludwig Institute for Cancer Research.
2007 (English)In: Biochimica et Biophysica Acta, ISSN 0006-3002, Vol. 1775, no 1, 21-62 p.Article, review/survey (Refereed) Published
Abstract [en]

Transforming growth factor-beta (TGF-beta) is a secreted polypeptide that signals via receptor serine/threonine kinases and intracellular Smad effectors. TGF-beta inhibits proliferation and induces apoptosis in various cell types, and accumulation of loss-of-function mutations in the TGF-beta receptor or Smad genes classify the pathway as a tumor suppressor in humans. In addition, various oncogenic pathways directly inactivate the TGF-beta receptor-Smad pathway, thus favoring tumor growth. On the other hand, all human tumors overproduce TGF-beta whose autocrine and paracrine actions promote tumor cell invasiveness and metastasis. Accordingly, TGF-beta induces epithelial-mesenchymal transition, a differentiation switch that is required for transitory invasiveness of carcinoma cells. Tumor-derived TGF-beta acting on stromal fibroblasts remodels the tumor matrix and induces expression of mitogenic signals towards the carcinoma cells, and upon acting on endothelial cells and pericytes, TGF-beta regulates angiogenesis. Finally, TGF-beta suppresses proliferation and differentiation of lymphocytes including cytolytic T cells, natural killer cells and macrophages, thus preventing immune surveillance of the developing tumor. Current clinical approaches aim at establishing novel cancer drugs whose mechanisms target the TGF-beta pathway. In conclusion, TGF-beta signaling is intimately implicated in tumor development and contributes to all cardinal features of tumor cell biology.

Place, publisher, year, edition, pages
2007. Vol. 1775, no 1, 21-62 p.
Keyword [en]
Cancer, Epithelial–mesenchymal transition, Metastasis, Smad, TGF-β, Tumor suppressor
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-21664DOI: 10.1016/j.bbcan.2006.06.004ISI: 000243317700003PubMedID: 16904831OAI: oai:DiVA.org:uu-21664DiVA: diva2:49437
Available from: 2007-01-02 Created: 2007-01-02 Last updated: 2011-03-29Bibliographically approved

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Pardali, KaterinaMoustakas, Aristidis
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