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Proteolytic Processing of CD44 and Its Implications in Cancer

Priscila Anhel Medrano-González1,2, Osmar Rivera-Ramírez1, Luis Felipe Montaño1

  • 1Lab. Inmunobiología, Depto. Biología Celular y Tisular, Facultad de Medicina, UNAM, Mexico, Mexico.

Stem Cells International
|January 28, 2021
PubMed

Insights

CD44 cleavage by metalloproteases generates cancer-driving CD44 isoforms. These fragments regulate cell cycle, metabolism, and stem cell markers, impacting cancer progression.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • CD44 is a transmembrane glycoprotein found in healthy and tumor tissues.
  • Structural modifications of CD44 influence its biological activity.
  • Metalloprotease-mediated cleavage of CD44 ectodomain is of significant interest.

Purpose of the Study:

  • To investigate the role of CD44 cleavage and its resulting isoforms in cancer.
  • To understand how CD44 fragments regulate signaling pathways involved in cancer development.
  • To explore the connection between CD44 fragments and stem cell markers.

Main Methods:

  • Analysis of CD44 structure and modifications.
  • Enzymatic cleavage assays using metalloproteases.
  • Study of alternative splice forms, specifically CD44v3 and CD44v6 isoforms.
  • Investigation of downstream signaling pathways including c-Src/STAT3, EGFR, ER, Wnt/β-catenin, and Hippo.

Main Results:

  • CD44 cleavage releases biologically active substrates.
  • Generated CD44v3 and v6 isoforms regulate transcriptional pathways crucial for cancer.
  • These pathways include c-Src/STAT3, EGFR, ER, Wnt/β-catenin, and Hippo signaling.
  • CD44 intracellular fragments regulate cell cycle, metabolism, and stem cell markers.

Conclusions:

  • CD44 cleavage is a key mechanism generating isoforms that drive cancer progression.
  • CD44 fragments play a critical role in regulating cellular processes and cancer-associated signaling.
  • CD44 remains a valuable prognostic marker, and its fragments offer insights into cancer biology and stemness.

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