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International Journal of Cell Biology
Volume 2013, Article ID 568931, 9 pages
Review Article

Regulation of the Ras-MAPK and PI3K-mTOR Signalling Pathways by Alternative Splicing in Cancer

1Department of Biochemistry and Molecular Biology, The Institute for Medical Research Israel-Canada, Hebrew University-Hadassah Medical School Ein Kerem, 91120 Jerusalem, Israel
2Institute of Molecular Genetics, National Research Council (IGM-CNR), Via Abbiategrasso 207, 27100 Pavia, Italy

Received 20 June 2013; Accepted 26 July 2013

Academic Editor: Claudio Sette

Copyright © 2013 Zahava Siegfried et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Alternative splicing is a fundamental step in regulation of gene expression of many tumor suppressors and oncogenes in cancer. Signalling through the Ras-MAPK and PI3K-mTOR pathways is misregulated and hyperactivated in most types of cancer. However, the regulation of the Ras-MAPK and PI3K-mTOR signalling pathways by alternative splicing is less well established. Recent studies have shown the contribution of alternative splicing regulation of these signalling pathways which can lead to cellular transformation, cancer development, and tumor maintenance. This review will discuss findings in the literature which describe new modes of regulation of components of the Ras-MAPK and PI3K-mTOR signalling pathways by alternative splicing. We will also describe the mechanisms by which signals from extracellular stimuli can be communicated to the splicing machinery and to specific RNA-binding proteins that ultimately control exon definition events.