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The dynamic roles of TGF-beta in cancer
Department of Molecular Cell Biology and Centre for Biomedical Genetics, Leiden University Medical Center, Postbus 9600, 2300 RC, Leiden, The Netherlands.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Ludwig Institute for Cancer Research.
2011 (English)In: Journal of Pathology, ISSN 0022-3417, E-ISSN 1096-9896, Vol. 223, no 2, 205-218 p.Article, review/survey (Refereed) Published
Abstract [en]

The transforming growth factor-beta (TGF-beta) signalling pathway plays a critical and dual role in the progression of human cancer. During the early phase of tumour progression, TGF-beta acts as a tumour suppressor, exemplified by deletions or mutations in the core components of the TGF-beta signalling pathway. On the contrary, TGF-beta also promotes processes that support tumour progression such as tumour cell invasion, dissemination, and immune evasion. Consequently, the functional outcome of the TGF-beta response is strongly context-dependent including cell, tissue, and cancer type. In this review, we describe the molecular signalling pathways employed by TGF-beta in cancer and how these, when perturbed, may lead to the development of cancer. Concomitantly with our increased appreciation of the molecular mechanisms that govern TGF-beta signalling, the potential to therapeutically target specific oncogenic sub-arms of the TGF-beta pathway increases. Indeed, clinical trials with systemic TGF-beta signalling inhibitors for treatment of cancer patients have been initiated. However, considering the important role of TGF-beta in cardiovascular and many other tissues, careful screening of patients is warranted to minimize unwanted on-target side effects.

Place, publisher, year, edition, pages
2011. Vol. 223, no 2, 205-218 p.
Keyword [en]
BMP, cancer, epithelial to mesenchymal transition, EMT, metastasis, signal transduction, Smad, TGF-beta, ubiquitin
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-144501DOI: 10.1002/path.2785ISI: 000285554600010PubMedID: 20957627OAI: oai:DiVA.org:uu-144501DiVA: diva2:393750
Available from: 2011-02-01 Created: 2011-01-31 Last updated: 2011-02-04Bibliographically approved

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