Repository logo
  • English
  • Deutsch
  • Español
  • Français
  • Log In
    New user? Click here to register.Have you forgotten your password?
Repository logo
  • Communities & Collections
  • Research Outputs
  • Fundings & Projects
  • Researchers
  • Statistics
  • English
  • Deutsch
  • Español
  • Français
  • Log In
    New user? Click here to register.Have you forgotten your password?
  1. Home
  2. CRIS
  3. Publication
  4. Alternative splicing downstream of EMT enhances phenotypic plasticity and malignant behavior in colon cancer
 
  • Details
Options

Alternative splicing downstream of EMT enhances phenotypic plasticity and malignant behavior in colon cancer

Journal
eLife
ISSN
2050-084X
Date Issued
2022-11-08
DOI
10.7554/eLife.82006
WoS ID
WOS:000961572800001
Abstract
Phenotypic plasticity allows carcinoma cells to transiently acquire the quasi-mesenchymal features necessary to detach from the primary mass and proceed along the invasion-metastasis cascade. A broad spectrum of epigenetic mechanisms is likely to cause the epithelial-to-mesenchymal (EMT) and mesenchymal-to-epithelial (MET) transitions necessary to allow local dissemination and distant metastasis. Here, we report on the role played by alternative splicing (AS) in eliciting phenotypic plasticity in epithelial malignancies with focus on colon cancer. By taking advantage of the coexistence of subpopulations of fully epithelial (EpCAMhi) and quasi-mesenchymal and highly metastatic (EpCAMlo) cells in conventional human cancer cell lines, we here show that the differential expression of ESRP1 and other RNA-binding proteins (RBPs) downstream of the EMT master regulator ZEB1 alters the AS pattern of a broad spectrum of targets including CD44 and NUMB, thus resulting in the generation of specific isoforms functionally associated with increased invasion and metastasis. Additional functional and clinical validation studies indicate that both the newly identified RBPs and the CD44s and NUMB2/4 splicing isoforms promote local invasion and distant metastasis and are associated with poor survival in colon cancer. The systematic elucidation of the spectrum of EMT-related RBPs and AS targets in epithelial cancers, apart from the insights in the mechanisms underlying phenotypic plasticity, will lead to the identification of novel and tumor-specific therapeutic targets.
OCDE Subjects

Medical and health sc...

Author(s)
Tong Xu
Mathijs Verhagen
Rosalie Joosten
Wenjie Sun
Andrea Sacchetti
Muñoz, Leonel  
Facultad de Medicina  
Véronique Orian-Rousseau
Riccardo Fodde

  • Cookie settings
  • Privacy policy
  • End User Agreement
  • Send Feedback

Hosting & Support by

Built with DSpace-CRIS software - Extension maintained and optimized by 4Science