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.

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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