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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
Summary
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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