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Detection of Alternative Splicing During Epithelial-Mesenchymal Transition
11:48

Detection of Alternative Splicing During Epithelial-Mesenchymal Transition

Published on: October 9, 2014

Differential splicing generates new transmembrane receptor and extracellular matrix-related targets for

Ulrich H Weidle1, Daniela Maisel, Stefan Klostermann

  • 1Roche Diagnostics, Division Pharma, Im Nonnenwald, Penzberg, Germany. ulrich.weidle@roche.com

Cancer Genomics & Proteomics
|October 8, 2011
PubMed

Insights

Alternative splicing deregulation in cancer creates novel therapeutic targets. These include specific protein isoforms in the transmembrane and extracellular matrix, offering new avenues for antibody-based cancer treatments.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Alternative splicing is frequently dysregulated in cancer, contributing to tumor growth.
  • Specific protein isoforms with restricted normal tissue expression and aberrant cancer expression are potential therapeutic targets.

Purpose of the Study:

  • To identify and characterize transmembrane and extracellular matrix protein isoforms generated by alternative splicing.
  • To evaluate these isoforms as potential targets for antibody-based cancer therapeutics.

Main Methods:

  • Analysis of alternative splicing patterns in normal versus cancerous tissues.
  • Focus on specific protein families including CD44, Claudin 18, L1CAM, EpCAM, fibronectin, tenascin, osteopontin, versican, FGFRs, EGFR, and RORN.

Main Results:

  • Identified specific alternatively spliced isoforms of transmembrane and extracellular matrix proteins.
  • These isoforms exhibit restricted expression in normal tissues but are deregulated in various cancers.
  • Examples include isoforms of CD44, Claudin 18, L1 cell adhesion molecule, epithelial cellular adhesion molecule, fibronectin, tenascin, osteopontin, versican, fibroblast growth factor receptors, epidermal growth factor receptor, and receptor d'origin nantais.

Conclusions:

  • Alternatively spliced isoforms of transmembrane and extracellular matrix proteins represent promising targets for antibody-based cancer therapies.
  • Targeting these cancer-specific isoforms could lead to more selective and effective treatments with reduced off-target effects.

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