The dynamic roles of TGF-beta in cancer
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
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.
BMP, cancer, epithelial to mesenchymal transition, EMT, metastasis, signal transduction, Smad, TGF-beta, ubiquitin
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-144501DOI: 10.1002/path.2785ISI: 000285554600010PubMedID: 20957627OAI: oai:DiVA.org:uu-144501DiVA: diva2:393750