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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
Published on: April 26, 2017
Regulation of the Ras-MAPK and PI3K-mTOR Signalling Pathways by Alternative Splicing in Cancer
Zahava Siegfried1, Serena Bonomi, Claudia Ghigna
1Department of Biochemistry and Molecular Biology, The Institute for Medical Research Israel-Canada, Hebrew University-Hadassah Medical School Ein Kerem, 91120 Jerusalem, Israel.
Abstract:
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.
Insights
Alternative splicing regulates gene expression in cancer by controlling key signaling pathways like Ras-MAPK and PI3K-mTOR. This review explores how alternative splicing impacts cancer development and maintenance.
Area of Science:
- Molecular Biology
- Cancer Biology
- Genetics
Background:
- Alternative splicing is crucial for regulating gene expression, particularly for tumor suppressors and oncogenes in cancer.
- Signaling through Ras-MAPK and PI3K-mTOR pathways is frequently hyperactivated in various cancers.
- The specific role of alternative splicing in regulating these critical cancer signaling pathways remains less understood.
Purpose of the Study:
- To review and discuss recent findings on alternative splicing regulation of Ras-MAPK and PI3K-mTOR signaling pathways in cancer.
- To elucidate the mechanisms by which extracellular signals influence the splicing machinery and RNA-binding proteins.
- To highlight how these splicing events contribute to cellular transformation, cancer development, and tumor progression.
Main Methods:
- Literature review of recent studies on alternative splicing and cancer signaling pathways.
- Analysis of mechanisms linking extracellular stimuli to RNA splicing machinery.
- Examination of the role of RNA-binding proteins in controlling alternative splicing events.
Main Results:
- Alternative splicing significantly contributes to the dysregulation of Ras-MAPK and PI3K-mTOR pathways in cancer.
- Specific alternative splicing events can drive cellular transformation, cancer initiation, and tumor maintenance.
- Extracellular signals are effectively communicated to the splicing machinery, influencing key regulatory proteins and exon definition.
Conclusions:
- Alternative splicing represents a critical regulatory layer for Ras-MAPK and PI3K-mTOR signaling in cancer.
- Understanding these splicing mechanisms offers potential new therapeutic strategies targeting cancer development and progression.
- Further research into the interplay between extracellular signals, RNA-binding proteins, and alternative splicing is warranted for cancer therapy.
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