Galectin-3 Is a Natural Binding Ligand of MCAM (CD146, MUC18) in Melanoma Cells and Their Interaction Promotes Melanoma Progression



Pang, Yaoyu, Maxwell, Ellen, Sindrewicz-Goral, Paulina, Shapanis, Andrew, Li, Shun, Morgan, Mark ORCID: 0000-0001-7728-9883 and Yu, Lu-Gang ORCID: 0000-0001-9641-3712
(2022) Galectin-3 Is a Natural Binding Ligand of MCAM (CD146, MUC18) in Melanoma Cells and Their Interaction Promotes Melanoma Progression. Biomolecules, 12 (10). p. 1451.

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Abstract

<jats:p>Melanoma cell adhesion molecule (MCAM, CD146, MUC18) is a heavily glycosylated transmembrane protein and a marker of melanoma metastasis. It is expressed in advanced primary melanoma and metastasis but rarely in benign naevi or normal melanocytes. More and more evidence has shown that activation of the MCAM on cell surface plays a vital role in melanoma progression and metastasis. However, the natural MCAM binding ligand that initiates MCAM activation in melanoma so far remains elusive. This study revealed that galectin-3, a galactoside-binding protein that is commonly overexpressed in many cancers including melanoma, is naturally associated with MCAM on the surface of both skin and uveal melanoma cells. Binding of galectin-3 to MCAM, via O-linked glycans on the MCAM, induces MCAM dimerization and clustering on cell surface and subsequent activation of downstream AKT signalling. This leads to the increases of a number of important steps in melanoma progression of cell proliferation, adhesion, migration, and invasion. Thus, galectin-3 is a natural binding ligand of MCAM in melanoma, and their interaction activates MCAM and promotes MCAM-mediated melanoma progression. Targeting the galectin-3–MCAM interaction may potentially be a useful therapeutic strategy for melanoma treatment.</jats:p>

Item Type: Article
Uncontrolled Keywords: galectin-3, MCAM/CD146, melanoma, cancer, galectin-ligand interaction
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 12 Oct 2022 09:33
Last Modified: 18 Jan 2023 20:36
DOI: 10.3390/biom12101451
Open Access URL: https://www.mdpi.com/2218-273X/12/10/1451/htm
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3165423