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EGF-Containing Membrane-Bound Mucins: A Hidden ErbB2 Targeting Pathway?
Maxime Liberelle1,2, Nicolas Jonckheere1,3, Patricia Melnyk1,2
1Univ. Lille, Inserm CHU Lille, UMR-S1172-JPArc-Centre de Recherche Jean-Pierre Aubert Neurosciences et Cancer, F-59000 Lille, France.
Journal of Medicinal Chemistry
|February 7, 2020
Summary
This study reveals that MUC3, MUC4, MUC12, MUC13, and MUC17 mucins share common evolutionary origins and structural features. These findings suggest potential therapeutic targets in ErbB2-related cancer signaling pathways.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Membrane-bound mucins are large O-glycoproteins implicated in epithelial cancers and inflammatory diseases.
- Specific mucins interact with receptor tyrosine kinase ErbB2, negatively impacting cancer prognosis and suggesting therapeutic potential.
Purpose of the Study:
- To investigate the common evolutionary origin and structural organization of MUC3, MUC4, MUC12, MUC13, and MUC17.
- To analyze the structure-function relationships of conserved domains in these mucins.
- To explore the therapeutic targeting of mucin-ErbB2 complexes in cancer.
Main Methods:
- Comparative analysis of evolutionary origins.
- Bioinformatic analysis of conserved EGF-like and SEA domains.
- Theoretical structure-function relationship modeling.
Main Results:
- MUC3, MUC4, MUC12, MUC13, and MUC17 share a common evolutionary history and structural organization.
- Conserved domains exhibit shared biological properties and potential unique functions.
- ErbB2-related signaling pathways involving these mucins are identified as potential therapeutic targets.
Conclusions:
- The studied membrane-bound mucins represent a cohesive group with shared ancestry and domain structures.
- Understanding their structure-function relationships provides insights into their roles in disease.
- Targeting mucin-ErbB2 complexes offers a promising strategy for cancer therapy.
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