Regulated intramembrane proteolysis of the TGF beta type I receptor conveys oncogenic signals
2014 (English)In: Future Oncology, ISSN 1479-6694, E-ISSN 1744-8301, Vol. 10, no 11, 1853-1861 p.Article in journal (Refereed) Published
Cancer cells produce high levels of TGF beta, a multipotent cytokine. Binding of TGF beta to its cell surface receptors, the transmembrane serine/threonine kinases T beta RII and T beta RI, causes phosphorylation and activation of intracellular latent Smad transcription factors. Nuclear Smads act in concert with specific transcription factors to reprogram epithelial cells to become invasive mesenchymal cells. TGF beta also propagates non-canonical signals, so it is crucial to have a better understanding of the underlying molecular mechanisms which favor this pathway. Here we highlight our recent discovery that TGF beta promotes the proteolytic cleavage of T beta RI in cancer cells, resulting in the liberation and nuclear translocation of its intracellular domain, acting as co-regulator to transcribe pro-invasive genes. This newly identified oncogenic TGF beta pathway resembles the Notch signaling pathway. We discuss our findings in relation to Notch and provide a short overview of other growth factors that transduce signals via nuclear translocation of their cell surface receptors.
Place, publisher, year, edition, pages
London, UK: Future Medicine Ltd , 2014. Vol. 10, no 11, 1853-1861 p.
cancer, nucleus TGF beta, proteolysis, receptors, signal transduction
Cancer and Oncology
IdentifiersURN: urn:nbn:se:umu:diva-96974DOI: 10.2217/FON.14.45ISI: 000344058100006OAI: oai:DiVA.org:umu-96974DiVA: diva2:769783